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This complex mediates intramembrane cleavage of amyloid precursor protein (APP) to generate ␤-amyloid protein (A␤) as well as other type 1" /> <meta property="article:author" content="https://independent.academia.edu/TakeshiTabira" /> <meta name="description" content="Presenilin 1 (PS1) forms the ␥-secretase complex with at least three components: nicastrin, APH-1, and PEN-2. 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window.loswp.willEdgeCache = false; window.loswp.work = {"work":{"id":59971412,"created_at":"2021-10-25T20:59:15.861-07:00","from_world_paper_id":181652608,"updated_at":"2024-11-24T12:00:12.453-08:00","_data":{"publisher":"FASEB","grobid_abstract":"Presenilin 1 (PS1) forms the ␥-secretase complex with at least three components: nicastrin, APH-1, and PEN-2. This complex mediates intramembrane cleavage of amyloid precursor protein (APP) to generate ␤-amyloid protein (A␤) as well as other type 1 transmembrane proteins. Although PS1 mutations linked to familial Alzheimer's disease influence these cleavages, their biological consequences have not been fully understood. In this study, we used mRNA differential display analysis to identify a gene, denoted adoplin-1/ORMDL-1, which displays significantly reduced expression in association with PS1 mutations. Adoplin-1 and two highly homologous genes (adoplin-2,-3) constitute a gene family that encodes transmembrane proteins. The mRNA and protein levels of adoplins (particularly adoplin-1,-2) were markedly elevated in PS-deficient fibroblasts, compared to wild-type cells. Moreover, knockdown of the three adoplins by RNA interference affected maturation of nicastrin and its association with PS1. Adoplin knockdown additionally resulted in elevated levels of APP C-terminal fragments and decreased A␤ production, suggestive of reduced ␥-secretase activity. Our data collectively indicate that adoplins are unique molecules with PS-related expression and functions that may play important role(s) in the maturation and activity of the ␥-secretase complex.","publication_date":"2007,,","publication_name":"The FASEB Journal","grobid_abstract_attachment_id":"73625813"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"A family of membrane proteins associated with presenilin expression and -secretase function","broadcastable":true,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [33151542]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "full_page_mobile_sutd_modal"; window.loswp.useOptimizedScribd4genScript = false; window.loginModal = {}; window.loginModal.appleClientId = 'edu.academia.applesignon'; window.userInChina = "false";</script><script defer="" src="https://accounts.google.com/gsi/client"></script><div class="ds-loswp-container"><div class="ds-work-card--grid-container"><div class="ds-work-card--container js-loswp-work-card"><div class="ds-work-card--cover"><div class="ds-work-cover--wrapper"><div class="ds-work-cover--container"><button class="ds-work-cover--clickable js-swp-download-button" data-signup-modal="{"location":"swp-splash-paper-cover","attachmentId":73625813,"attachmentType":"pdf"}"><img alt="First page of “A family of membrane proteins associated with presenilin expression and -secretase function”" class="ds-work-cover--cover-thumbnail" src="https://0.academia-photos.com/attachment_thumbnails/73625813/mini_magick20211025-16765-3gn7yi.png?1635220861" /><img alt="PDF Icon" class="ds-work-cover--file-icon" src="//a.academia-assets.com/images/single_work_splash/adobe_icon.svg" /><div class="ds-work-cover--hover-container"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span><p>Download Free PDF</p></div><div class="ds-work-cover--ribbon-container">Download Free PDF</div><div class="ds-work-cover--ribbon-triangle"></div></button></div></div></div><div class="ds-work-card--work-information"><h1 class="ds-work-card--work-title">A family of membrane proteins associated with presenilin expression and -secretase function</h1><div class="ds-work-card--work-authors ds-work-card--detail"><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="33151542" href="https://independent.academia.edu/TakeshiTabira"><img alt="Profile image of Takeshi Tabira" class="ds-work-card--author-avatar" src="//a.academia-assets.com/images/s65_no_pic.png" />Takeshi Tabira</a></div><div class="ds-work-card--detail"><p class="ds-work-card--detail ds2-5-body-sm">2007, The FASEB Journal</p><div class="ds-work-card--work-metadata"><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">visibility</span><p class="ds2-5-body-sm" id="work-metadata-view-count">…</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">description</span><p class="ds2-5-body-sm">9 pages</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">link</span><p class="ds2-5-body-sm">1 file</p></div></div><script>(async () => { const workId = 59971412; const worksViewsPath = "/v0/works/views?subdomain_param=api&work_ids%5B%5D=59971412"; const getWorkViews = async (workId) => { const response = await fetch(worksViewsPath); if (!response.ok) { throw new Error('Failed to load work views'); } const data = await response.json(); return data.views[workId]; }; // Get the view count for the work - we send this immediately rather than waiting for // the DOM to load, so it can be available as soon as possible (but without holding up // the backend or other resource requests, because it's a bit expensive and not critical). const viewCount = await getWorkViews(workId); const updateViewCount = (viewCount) => { try { const viewCountNumber = parseInt(viewCount, 10); if (viewCountNumber === 0) { // Remove the whole views element if there are zero views. document.getElementById('work-metadata-view-count')?.parentNode?.remove(); return; } const commaizedViewCount = viewCountNumber.toLocaleString(); const viewCountBody = document.getElementById('work-metadata-view-count'); if (!viewCountBody) { throw new Error('Failed to find work views element'); } viewCountBody.textContent = `${commaizedViewCount} views`; } catch (error) { // Remove the whole views element if there was some issue parsing. document.getElementById('work-metadata-view-count')?.parentNode?.remove(); throw new Error(`Failed to parse view count: ${viewCount}`, error); } }; // If the DOM is still loading, wait for it to be ready before updating the view count. if (document.readyState === "loading") { document.addEventListener('DOMContentLoaded', () => { updateViewCount(viewCount); }); // Otherwise, just update it immediately. } else { updateViewCount(viewCount); } })();</script></div><p class="ds-work-card--work-abstract ds-work-card--detail ds2-5-body-md">Presenilin 1 (PS1) forms the ␥-secretase complex with at least three components: nicastrin, APH-1, and PEN-2. This complex mediates intramembrane cleavage of amyloid precursor protein (APP) to generate ␤-amyloid protein (A␤) as well as other type 1 transmembrane proteins. Although PS1 mutations linked to familial Alzheimer's disease influence these cleavages, their biological consequences have not been fully understood. In this study, we used mRNA differential display analysis to identify a gene, denoted adoplin-1/ORMDL-1, which displays significantly reduced expression in association with PS1 mutations. Adoplin-1 and two highly homologous genes (adoplin-2,-3) constitute a gene family that encodes transmembrane proteins. The mRNA and protein levels of adoplins (particularly adoplin-1,-2) were markedly elevated in PS-deficient fibroblasts, compared to wild-type cells. Moreover, knockdown of the three adoplins by RNA interference affected maturation of nicastrin and its association with PS1. Adoplin knockdown additionally resulted in elevated levels of APP C-terminal fragments and decreased A␤ production, suggestive of reduced ␥-secretase activity. Our data collectively indicate that adoplins are unique molecules with PS-related expression and functions that may play important role(s) in the maturation and activity of the ␥-secretase complex.</p><div class="ds-work-card--button-container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--work-card","attachmentId":73625813,"attachmentType":"pdf","workUrl":"https://www.academia.edu/59971412/A_family_of_membrane_proteins_associated_with_presenilin_expression_and_secretase_function"}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--work-card","attachmentId":73625813,"attachmentType":"pdf","workUrl":"https://www.academia.edu/59971412/A_family_of_membrane_proteins_associated_with_presenilin_expression_and_secretase_function"}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div><div class="ds-signup-banner-trigger-container"><div class="ds-signup-banner-trigger ds-signup-banner-trigger-control"></div></div><div class="ds-signup-banner ds-signup-banner-control"><div id="ds-signup-banner-close-button"><button class="ds2-5-button ds2-5-button--secondary ds2-5-button--inverse"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">close</span></button></div><div class="ds-signup-banner-ctas"><img src="//a.academia-assets.com/images/academia-logo-capital-white.svg" /><h4 class="ds2-5-heading-serif-sm">Sign up for access to the world's latest research</h4><button class="ds2-5-button ds2-5-button--inverse ds2-5-button--full-width js-swp-download-button" data-signup-modal="{"location":"signup-banner"}">Sign up for free<span class="material-symbols-outlined" style="font-size: 20px" translate="no">arrow_forward</span></button></div><div class="ds-signup-banner-divider"></div><div class="ds-signup-banner-reasons"><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Get notified about relevant papers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Save papers to use in your research</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Join the discussion with peers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Track your impact</span></div></div></div><script>(() => { // Set up signup banner show/hide behavior: // 1. 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To determine which subcellular compartments are potential source(s) of released A␤42, we compared the levels and spatial segregation of intracellular A␤40 and A␤42 peptides between N2a neuroblastoma cells doubly transfected with the "Swedish" familial Alzheimer's disease-linked amyloid precursor protein variant and either wild-type PS1 (PS1 wt ) or familial Alzheimer's disease-linked ⌬9 mutant PS1 (PS1 ⌬9 ). As expected, PS1 ⌬9 -expressing cells had dramatically higher levels of intracellular A␤42 than did cells expressing PS1 wt . However, the highest levels of A␤42 colocalized not with endoplasmic reticulum or Golgi markers but with rab8, a marker for trans-Golgi network (TGN)-to-plasma membrane (PM) transport vesicles. We show that PS1 mutants are capable of causing accumulation of A␤42 in late compartments of the secretory pathway, generating there a readily releasable source of A␤42. Our findings indicate that PS1 "bioactivity" localizes to the vicinity of the TGN and/or PM and reconcile the apparent discrepancy between the preponderant concentration of PS1 protein in proximal compartments of the secretory pathway and the recent findings that PS1 "bioactivity" can control ␥-secretase-like processing of another transmembrane substrate, Notch, at or near the PM.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Mutant Presenilin 1 Increases the Levels of Alzheimer Amyloid β-Peptide Aβ42 in Late Compartments of the Constitutive Secretory Pathway","attachmentId":45232279,"attachmentType":"pdf","work_url":"https://www.academia.edu/13538972/Mutant_Presenilin_1_Increases_the_Levels_of_Alzheimer_Amyloid_%CE%B2_Peptide_A%CE%B242_in_Late_Compartments_of_the_Constitutive_Secretory_Pathway","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/13538972/Mutant_Presenilin_1_Increases_the_Levels_of_Alzheimer_Amyloid_%CE%B2_Peptide_A%CE%B242_in_Late_Compartments_of_the_Constitutive_Secretory_Pathway"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="1" data-entity-id="61938490" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/61938490/Deficiency_of_presenilin_1_inhibits_the_normal_cleavage_of_amyloid_precursor_protein">Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="50662016" href="https://independent.academia.edu/hvanderstichele">hugo vanderstichele</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Nature, 1998</p><p class="ds-related-work--abstract ds2-5-body-sm">Point mutations in the presenilin-1 gene (PS1) are a major cause of familial Alzheimer&#39;s disease. They result in a selective increase in the production of the amyloidogenic peptide amyloid-beta(1-42) by proteolytic processing of the amyloid precursor protein (APP). Here we investigate whether PS1 is also involved in normal APP processing in neuronal cultures derived from PS1-deficient mouse embryos. Cleavage by alpha- and beta-secretase of the extracellular domain of APP was not affected by the absence of PS1, whereas cleavage by gamma-secretase of the transmembrane domain of APP was prevented, causing carboxyl-terminal fragments of APP to accumulate and a fivefold drop in the production of amyloid peptide. Pulse-chase experiments indicated that PS1 deficiency specifically decreased the turnover of the membrane-associated fragments of APP. As in the regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor, PS1 appears to facilitate a proteolyt...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein","attachmentId":74843309,"attachmentType":"pdf","work_url":"https://www.academia.edu/61938490/Deficiency_of_presenilin_1_inhibits_the_normal_cleavage_of_amyloid_precursor_protein","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/61938490/Deficiency_of_presenilin_1_inhibits_the_normal_cleavage_of_amyloid_precursor_protein"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="2" data-entity-id="84234636" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/84234636/Cell_surface_expression_of_the_Alzheimer_disease_related_presenilin_proteins">Cell surface expression of the Alzheimer disease-related presenilin proteins</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="35510034" href="https://independent.academia.edu/NazneenDewji">Nazneen Dewji</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Proceedings of the National Academy of Sciences, 1997</p><p class="ds-related-work--abstract ds2-5-body-sm">The presenilin proteins PS-1 and PS-2 are crucially involved in Alzheimer disease (AD), but their molecular functions are not known. They are integral membrane proteins, but whether they can be expressed at the surface of cells has been in dispute. Here we show by immunofluorescence experiments, using anti-peptide antibodies specific for either PS-1 or PS-2, that live cultured DAMI cells and differentiated human NT2N neuronal cells are specifically immunolabeled for their endogenous as well as transfected presenilins, although the cells cannot be immunolabeled for their intracellular tubulin, unless they are first fixed and permeabilized. These and other results establish that portions of the presenilins are indeed expressed at the surfaces of these cells. These findings support our previous proposal that the presenilins on the surface of a cell engage in intercellular interactions with the β-amyloid precursor protein on the surface of a neighboring cell, as a critical step in the m...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Cell surface expression of the Alzheimer disease-related presenilin proteins","attachmentId":89328845,"attachmentType":"pdf","work_url":"https://www.academia.edu/84234636/Cell_surface_expression_of_the_Alzheimer_disease_related_presenilin_proteins","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/84234636/Cell_surface_expression_of_the_Alzheimer_disease_related_presenilin_proteins"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="13538977" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/13538977/%CE%B1_Secretase_Derived_Product_of_%CE%B2_Amyloid_Precursor_Protein_Is_Decreased_by_Presenilin_1_Mutations_Linked_to_Familial_Alzheimers_Disease">α-Secretase-Derived Product of β-Amyloid Precursor Protein Is Decreased by Presenilin 1 Mutations Linked to Familial Alzheimer's Disease</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32733464" href="https://landaverde.academia.edu/Fr%C3%A9d%C3%A9ricChecler">Frédéric Checler</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Neurochemistry, 2002</p><p class="ds-related-work--abstract ds2-5-body-sm">Recent reports indicate that missense mutations on presenilin (PS) 1 are likely responsible for the main early-onset familial forms of Alzheimer's disease (FAD). Consensual data obtained through distinct histopathological, cell biology, and molecular biology approaches have led to the conclusion that these PSi mutations clearly trigger an increased production of the 42amino-acid-long species of /1-amyloid peptide (A/I). Here we show that overexpression of wild-type PSi in HK293 cells increases A/I40 secretion. By contrast, FAD-linked mutants of PSi trigger increased secretion of both A/340 and A/342 but clearly favor the production of the latter species. We also demonstrate that overexpression of the wild-type PSi augments the a-secretase-derived C-terminally truncated fragment of /3-amyloid precursor protein (APPc~)recovery, whereas transfectants expressing mutated PSi secrete drastically lower amounts of APPcr when compared with cells expressing wild-type PSi . This decrease was also observed when comparing double transfectants overexpressing wild-type /3-amyloid precursor protein and either PSi or its mutated congener Ml 46V-PS1. Altogether, our data indicate that PS mutations linked to FAD not only trigger an increased ratio of A/342 over total A/I secretion but concomitantly downregulate the production of APPa. Key Words: Familial Alzheimer's disease-Presenilin 1 -a-Secretase-APPa-~3-Amyloidpeptide-/3-Amyloid precursor protein.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"α-Secretase-Derived Product of β-Amyloid Precursor Protein Is Decreased by Presenilin 1 Mutations Linked to Familial Alzheimer's Disease","attachmentId":45232255,"attachmentType":"pdf","work_url":"https://www.academia.edu/13538977/%CE%B1_Secretase_Derived_Product_of_%CE%B2_Amyloid_Precursor_Protein_Is_Decreased_by_Presenilin_1_Mutations_Linked_to_Familial_Alzheimers_Disease","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/13538977/%CE%B1_Secretase_Derived_Product_of_%CE%B2_Amyloid_Precursor_Protein_Is_Decreased_by_Presenilin_1_Mutations_Linked_to_Familial_Alzheimers_Disease"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="122416072" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/122416072/Inhibiting_Amyloid_Precursor_Protein_C_terminal_Cleavage_Promotes_an_Interaction_with_Presenilin_1">Inhibiting Amyloid Precursor Protein C-terminal Cleavage Promotes an Interaction with Presenilin 1</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="320114875" href="https://independent.academia.edu/ErinHolmes19">Erin Holmes</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Biological Chemistry, 2000</p><p class="ds-related-work--abstract ds2-5-body-sm">Presenilin 1 (PS1) plays a pivotal role in the production of the amyloid-␤ protein, which is central to the pathogenesis of Alzheimer's disease. It has been demonstrated that PS1 regulates the ␥-secretase proteolysis of the amyloid precursor protein (APP) C-terminal fragment (APP-C100), which is the final step in amyloid-␤ protein production. The mechanism and detailed pathway of this PS1 activity has yet to be fully resolved, but it may be due to a presenilin-controlled trafficking of the APP fragment or possibly an inherent PS1 proteolytic activity. We have investigated the possibility of a direct interaction of PS1 and the APP-C100 within the high molecular mass presenilin complex. However, the APP-C100 is rapidly degraded, and if it forms, then any PS1⅐APP complex is likely to be very transitory. To circumvent this problem, we have utilized the protease inhibitor N-acetyl-leucyl-norleucinal (LLnL) and the lysosomotropic agent NH 4 Cl, which inhibits the turnover of the APP-C100. Under these conditions, levels of the fragment increased appreciably, and as shown by glycerol gradient analysis, the APP-C100 shifted to a higher molecular mass complex that overlapped with PS1. Immunoprecipitation studies demonstrated that a significant population of the APP-C100 co-precipitated with PS1. These findings suggest that PS1 may mediate the shuttling of APP fragments and/or facilitate their presentation for ␥-secretase cleavage through a direct interaction. Alzheimer's disease (AD) 1 is characterized by extensive neuronal loss culminating in the presentation of dementia. One of</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Inhibiting Amyloid Precursor Protein C-terminal Cleavage Promotes an Interaction with Presenilin 1","attachmentId":117083345,"attachmentType":"pdf","work_url":"https://www.academia.edu/122416072/Inhibiting_Amyloid_Precursor_Protein_C_terminal_Cleavage_Promotes_an_Interaction_with_Presenilin_1","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/122416072/Inhibiting_Amyloid_Precursor_Protein_C_terminal_Cleavage_Promotes_an_Interaction_with_Presenilin_1"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="28970890" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/28970890/Interaction_between_amyloid_precursor_protein_and_presenilins_in_mammalian_cells_Implications_for_the_pathogenesis_of_Alzheimer_disease">Interaction between amyloid precursor protein and presenilins in mammalian cells: Implications for the pathogenesis of Alzheimer disease</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="733194" href="https://ttuhsc.academia.edu/RuthPerez">Ruth Perez</a></div><p class="ds-related-work--abstract ds2-5-body-sm">Mutations in the presenilin 1 (PS1) and pre-senilin 2 (PS2) genes increase the production of the highly amyloidogenic 42-residue form of amyloid-protein (A 42) in a variety of cell lines and transgenic mice. To elucidate the molecular mechanism of this effect, wild-type (wt) or mutant PS1 and PS2 genes were stably transfected into Chinese hamster ovary cells expressing endogenous or transfected-amyloid precursor protein (APP). By immunoprecipita-tionWestern blot analysis, APP was consistently found to coimmunoprecipitate with PS1 or PS2 proteins. Several distinct PS1, PS2, or APP antibodies precipitated PS–APP complexes that were detectable by blotting with either APP or PS antibodies. Importantly, complex formation could be detected at endogenous protein levels in nontransfected cells. In various Chinese hamster ovary cell lines, the amounts of APP coprecipitated by PS antibodies were proportional to the expression levels of both APP and PS. APP–PS complexes also were recovered from human 293 and HS683 cells. Full mat-uration of APP was not required for the interaction; most APP molecules complexed with PS were solely N-glycosylated. Treatment of cells with brefeldin A or incubation at 20°C did not block complex formation, suggesting that the association between APP and PS occurs in part in the endoplasmic reticulum. Complex formation was detected for both wt and mutant PS and APP proteins. Deletion of the APP C-terminal domain did not abrogate complex formation, suggesting that the interaction does not occur in the cytoplasmic domains of the proteins. Our results demonstrate that wt and mutant PS1 and PS2 proteins form complexes with APP in living cells, strongly supporting the hypothesis that mutant PS interacts with APP in a way that enhances the intramembranous proteolysis of the latter by a-secretase cleaving at A 42 .</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Interaction between amyloid precursor protein and presenilins in mammalian cells: Implications for the pathogenesis of Alzheimer disease","attachmentId":49412176,"attachmentType":"pdf","work_url":"https://www.academia.edu/28970890/Interaction_between_amyloid_precursor_protein_and_presenilins_in_mammalian_cells_Implications_for_the_pathogenesis_of_Alzheimer_disease","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/28970890/Interaction_between_amyloid_precursor_protein_and_presenilins_in_mammalian_cells_Implications_for_the_pathogenesis_of_Alzheimer_disease"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="28426425" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/28426425/Presenilin_1_protein_expression_in_familial_and_sporadic_Alzheimers_disease">Presenilin-1 protein expression in familial and sporadic Alzheimer's disease</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="53298562" href="https://setonhall.academia.edu/DavidNochlin">David Nochlin</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Annals of Neurology, 1997</p><p class="ds-related-work--abstract ds2-5-body-sm">Mutations of the presenilin PSI and PS2 genes are closely linked to aggressive forms of early-onset (<60 years) familial Alzheimer's disease. A highly specific monoclonal antibody was developed to identify and characterize the native PSI protein. Western blot analyses revealed a predominant 32-kd immunoreactive polypeptide in a variety of samples, including PC12 cells transfected with human PSI complementary DNA, brain biopsy specimens from demented patients, and postmortem samples of frontal neocortex from early-onset familial Alzheimer's disease cases (PSI and PS2), lateonset sporadic Alzheimer's disease cases, and cases of other degenerative disorders. This truncated polypeptide contains the N-terminus of PS1 and appeared unchanged across cases. In 2 early-onset cases linked to missense mutations in the PSI gene, a PSI immunoreactive protein (-49 kd) accumulated in the frontal cortex. This protein was similar in size to full-length PSI protein present in transfected cells overexpressing PSI complementary DNA, and in lymphocytes from an affected individual with a deletion of exon 9 of the PSI gene, suggesting that mutations of the PSI gene perturb the endoproteolytic processing of the protein. Immunohistochemical studies of control brains revealed that PS 1 is expressed primarily in neurons, with the protein localized in the soma and dendritic processes. In contrast, PSI showed striking localization to the neuropathology in early-onset familial Alzheimer's disease and sporadic Alzheimer's disease cases. PSI immunoreactivity was present in the neuritic component of senile plaques as well as in neurofibrillary tangles. Localization of PSI immunoreactivity in familial and sporadic Alzheimer's disease suggests that genetically heterogeneous forms of the disease share a common pathophysiology involving PSI protein. EJ. Presenilin-1 protein expression in familial and sporadic Alzheimer's disease. Ann Neurol 1997;4 1:742-753 _ _ _ _ _ _~. Alzheimer's disease (AD) is heterogeneous, with several distinct genes linked to familial (FAD) and sporadic forms of the disorder. The apolipoprotein E (Apo E) ~4 allele is a well-established risk factor for late-onset FAD, as well as for the more commonly occurring sporadic forms [ 11. Early-onset FAD accounts for about 5 to 10% of all cases, and is notable clinically for a highly aggressive nature with earlier age at onset (typically <60 years), shorter duration of survival, and more prominent myoclonus, seizures, and aphasia 12-71. The pathological features of FAD are similar to those of sporadic AD with abundant amyloid plaques and neurofibrillary tangles [G, 71. The autosomal dominant patterns of inheritance of the early-onset forms have enabled identification of three distinct genes linked to the disease, including tht. amyloid precursor protein (APP) gene on chromosome 21 [S-lO], presenilin-1 (PSI, origiiially termed S182) on chromo-some 14 [l l-151, and presenilin-2 (PS2, originally termed STM2 or E5-1) on chromosome 1 [15-171.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Presenilin-1 protein expression in familial and sporadic Alzheimer's disease","attachmentId":48772434,"attachmentType":"pdf","work_url":"https://www.academia.edu/28426425/Presenilin_1_protein_expression_in_familial_and_sporadic_Alzheimers_disease","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/28426425/Presenilin_1_protein_expression_in_familial_and_sporadic_Alzheimers_disease"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="75415654" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/75415654/Presenilin_mutation_A_deadly_first_hit_in_Alzheimer_disease">Presenilin mutation: A deadly first hit in Alzheimer disease</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="70315238" href="https://independent.academia.edu/PaulaMoreira42">Paula Moreira</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Free Radical Biology and Medicine, 2006</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Presenilin mutation: A deadly first hit in Alzheimer disease","attachmentId":83193250,"attachmentType":"pdf","work_url":"https://www.academia.edu/75415654/Presenilin_mutation_A_deadly_first_hit_in_Alzheimer_disease","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/75415654/Presenilin_mutation_A_deadly_first_hit_in_Alzheimer_disease"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="113737502" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/113737502/Presenilin_structure_function_and_role_in_Alzheimer_disease">Presenilin structure, function and role in Alzheimer disease</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="51729472" href="https://independent.academia.edu/DunShengYang">Dun-Sheng Yang</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2000</p><p class="ds-related-work--abstract ds2-5-body-sm">Numerous missense mutations in the presenilins are associated with the autosomal dominant form of familial Alzheimer disease. Presenilin genes encode polytopic transmembrane proteins, which are processed by proteolytic cleavage and form high-molecular-weight complexes under physiological conditions. The presenilins have been suggested to be functionally involved in developmental morphogenesis, unfolded protein responses and processing of selected proteins including the L-amyloid precursor protein. Although the underlying mechanism by which presenilin mutations lead to development of Alzheimer disease remains elusive, one consistent mutational effect is an overproduction of long-tailed amyloid L-peptides. Furthermore, presenilins interact with L-catenin to form presenilin complexes, and the physiological and mutational effects are also observed in the catenin signal transduction pathway.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Presenilin structure, function and role in Alzheimer disease","attachmentId":110622902,"attachmentType":"pdf","work_url":"https://www.academia.edu/113737502/Presenilin_structure_function_and_role_in_Alzheimer_disease","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/113737502/Presenilin_structure_function_and_role_in_Alzheimer_disease"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="64584947" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/64584947/APH1_PEN2_and_Nicastrin_increase_A%CE%B2_levels_and_%CE%B3_secretase_activity">APH1, PEN2, and Nicastrin increase Aβ levels and γ-secretase activity</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33636516" href="https://musc.academia.edu/KSambamurti">Kumar Sambamurti</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2003</p><p class="ds-related-work--abstract ds2-5-body-sm">A major component of the amyloid plaque core in AlzheimerÕs disease (AD) is the 40-42-residue amyloid b peptide (Ab). Mutations linked to AD such as those in presenilins 1 (PS1) and 2 (PS2) invariably increase the longer Ab42 species that forms neurotoxic oligomers. It is believed that PS1/2 constitute the catalytic subunit of the c-secretase responsible for the final step in Ab biogenesis. Recent genetic studies have identified a number of additional genes encoding APH1a, APH1b, PEN2, and Nicastrin proteins, which are part of the c-secretase complex with PS1. Further, knockout studies using RNAi showed that these components are essential for c-secretase activity. However, the nature of c-secretase and how the aforementioned proteins regulate its activity are still incompletely understood. Here we present evidence that unlike PS1, overexpression of these proteins can increase the levels of Ab, suggesting that these proteins are limiting for c-secretase activity. In addition, our studies also suggest that the presenilin partners regulate the relative levels of Ab40 and Ab42.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"APH1, PEN2, and Nicastrin increase Aβ levels and γ-secretase activity","attachmentId":76554336,"attachmentType":"pdf","work_url":"https://www.academia.edu/64584947/APH1_PEN2_and_Nicastrin_increase_A%CE%B2_levels_and_%CE%B3_secretase_activity","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/64584947/APH1_PEN2_and_Nicastrin_increase_A%CE%B2_levels_and_%CE%B3_secretase_activity"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":73625813,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":73625813,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_73625813" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. You can download the paper by clicking the button above.</p></div></div></div></div><div class="ds-sidebar--container js-work-sidebar"><div class="ds-related-content--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="0" data-entity-id="84348977" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/84348977/Carboxyl_terminal_Fragments_of_Alzheimer_%CE%B2_Amyloid_Precursor_Protein_Accumulate_in_Restricted_and_Unpredicted_Intracellular_Compartments_in_Presenilin_1_deficient_Cells">Carboxyl-terminal Fragments of Alzheimer β-Amyloid Precursor Protein Accumulate in Restricted and Unpredicted Intracellular Compartments in Presenilin 1-deficient Cells</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" 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href="https://www.academia.edu/21088582/Mutated_presenilins_and_Alzheimers_disease_the_culprit_could_be_calcium_signaling"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="2" data-entity-id="84470113" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/84470113/Cloning_of_Presenilin_2_cDNA_and_Construction_of_Vectors_Carrying_Effective_Mutations_in_the_Pathogenesis_of_Familial_Alzheimers_Disease">Cloning of Presenilin 2 cDNA and Construction of Vectors Carrying Effective Mutations in the Pathogenesis of Familial Alzheimer's Disease</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="57228871" href="https://independent.academia.edu/BYoke%C5%9F">Baki Yokeş</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Electrica, 2018</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Cloning of Presenilin 2 cDNA and Construction of Vectors Carrying Effective Mutations in the Pathogenesis of Familial Alzheimer's Disease","attachmentId":89483807,"attachmentType":"pdf","work_url":"https://www.academia.edu/84470113/Cloning_of_Presenilin_2_cDNA_and_Construction_of_Vectors_Carrying_Effective_Mutations_in_the_Pathogenesis_of_Familial_Alzheimers_Disease","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/84470113/Cloning_of_Presenilin_2_cDNA_and_Construction_of_Vectors_Carrying_Effective_Mutations_in_the_Pathogenesis_of_Familial_Alzheimers_Disease"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="3" data-entity-id="77629409" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/77629409/An_insight_into_Alzheimer_s_disease_and_its_on_setting_novel_genes">An insight into Alzheimer’s disease and its on-setting novel genes</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="110680190" href="https://independent.academia.edu/shafrasmohamed">mohamed shafras</a></div><p 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class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="6" data-entity-id="77561685" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/77561685/Multiple_Effects_of_Aspartate_Mutant_Presenilin_1_on_the_Processing_and_Trafficking_of_Amyloid_Precursor_Protein">Multiple Effects of Aspartate Mutant Presenilin 1 on the Processing and Trafficking of Amyloid Precursor Protein</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="45103752" href="https://independent.academia.edu/JamesLah">James Lah</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Biological Chemistry, 2001</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" 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ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/99357002/Familial_Alzheimer_Disease_linked_Presenilin_1_Variants_Enhance_Production_of_Both_A%CE%B21_40_and_A%CE%B21_42_Peptides_That_Are_Only_Partially_Sensitive_to_a_Potent_Aspartyl_Protease_Transition_State_Inhibitor_of_%CE%B3_Secretase_">Familial Alzheimer Disease-linked Presenilin 1 Variants Enhance Production of Both Aβ1–40 and Aβ1–42 Peptides That Are Only Partially Sensitive to a Potent Aspartyl Protease Transition State Inhibitor of “γ-Secretase”</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33040587" href="https://independent.academia.edu/GeorgiaDolios">Georgia Dolios</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Biological Chemistry, 2002</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" 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href="https://www.academia.edu/99357002/Familial_Alzheimer_Disease_linked_Presenilin_1_Variants_Enhance_Production_of_Both_A%CE%B21_40_and_A%CE%B21_42_Peptides_That_Are_Only_Partially_Sensitive_to_a_Potent_Aspartyl_Protease_Transition_State_Inhibitor_of_%CE%B3_Secretase_"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="9" data-entity-id="5411347" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/5411347/Presenilin_Dependent_Transcriptional_Control_of_the_A%CE%B2_Degrading_Enzyme_Neprilysin_by_Intracellular_Domains_of_%CE%B2APP_and_APLP">Presenilin-Dependent Transcriptional Control of the Aβ-Degrading Enzyme Neprilysin by Intracellular Domains of βAPP and APLP</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="7557734" href="https://independent.academia.edu/VincentBruno">Bruno Vincent</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Neuron, 2005</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Presenilin-Dependent Transcriptional Control of the Aβ-Degrading Enzyme Neprilysin by Intracellular Domains of βAPP and APLP","attachmentId":49302711,"attachmentType":"pdf","work_url":"https://www.academia.edu/5411347/Presenilin_Dependent_Transcriptional_Control_of_the_A%CE%B2_Degrading_Enzyme_Neprilysin_by_Intracellular_Domains_of_%CE%B2APP_and_APLP","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free 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class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="222687" href="https://uni-freiburg.academia.edu/RalfBaumeister">Ralf Baumeister</a></div><p class="ds-related-work--metadata ds2-5-body-xs">European Archives of Psychiatry and Clinical …, 1999</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The Biological and Pathological Function of Presenilin Proteinssimple Cell Systems and a Worm In Alzheimer's Disease Research","attachmentId":51270715,"attachmentType":"pdf","work_url":"https://www.academia.edu/724912/The_Biological_and_Pathological_Function_of_Presenilin_Proteins_simple_Cell_Systems_and_a_Worm_In_Alzheimers_Disease_Research","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span 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disease and leads to death as early as the age of 28 years</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="58245632" href="https://independent.academia.edu/Frangione">B. Frangione</a><span>, </span><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="58189284" href="https://independent.academia.edu/WieslawDowjat">Wieslaw Dowjat</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Neuroreport, 1998</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"A novel Polish presenilin-1 mutation (P117L) is associated with familial Alzheimer's disease and leads to death as early as the age of 28 years","attachmentId":50972895,"attachmentType":"pdf","work_url":"https://www.academia.edu/30529693/A_novel_Polish_presenilin_1_mutation_P117L_is_associated_with_familial_Alzheimers_disease_and_leads_to_death_as_early_as_the_age_of_28_years","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span 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precursor protein to the presenilins induces intercellular signaling: Its significance for Alzheimer's disease</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="35510034" href="https://independent.academia.edu/NazneenDewji">Nazneen Dewji</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Proceedings of the National Academy of Sciences of the United States of America, 1998</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Specific intercellular binding of the -amyloid precursor protein to the presenilins induces intercellular signaling: Its significance for Alzheimer's 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data-collection-position="13" data-entity-id="14878095" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/14878095/Regulated_intramembrane_proteolysis_of_amyloid_precursor_protein_and_regulation_of_expression_of_putative_target_genes">Regulated intramembrane proteolysis of amyloid precursor protein and regulation of expression of putative target genes</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33852231" href="https://ulaval.academia.edu/S%C3%A9bastienH%C3%A9bert">Sébastien Hébert</a></div><p class="ds-related-work--metadata ds2-5-body-xs">EMBO reports, 2006</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Regulated intramembrane proteolysis of amyloid 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