Evidence that production and release of amyloid beta-protein involves the endocytic pathway.
Edward H. Koo,Sharon L. Squazzo +1 more
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TLDR
It is hypothesized that the internalization of cell surface amyloid precursor protein (beta PP) via coated pit-mediated endocytosis is one pathway leading to A beta generation and release into medium.About:
This article is published in Journal of Biological Chemistry.The article was published on 1994-07-01 and is currently open access. It has received 1031 citations till now. The article focuses on the topics: Senile plaques & Amyloid precursor protein.read more
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Journal ArticleDOI
Alzheimer's Disease: Genes, Proteins, and Therapy
TL;DR: Evidence that the presenilin proteins, mutations in which cause the most aggressive form of inherited AD, lead to altered intramembranous cleavage of the beta-amyloid precursor protein by the protease called gamma-secretase has spurred progress toward novel therapeutics and provided discrete biochemical targets for drug screening and development.
Journal ArticleDOI
Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE.
Robert Vassar,Brian D. Bennett,Safura Babu-Khan,Steve Kahn,Elizabeth A. Mendiaz,Paul Denis,David B. Teplow,Sandra Ross,Patricia Amarante,Richard Loeloff,Yi Luo,Seth Fisher,Janis Fuller,Steven P. Edenson,Jackson Lile,Mark A. Jarosinski,Anja Leona Biere,Eileen Curran,Teresa L. Burgess,Jean Claude Louis,Frank H. Collins,James J. S. Treanor,Gary Rogers,Martin Citron +23 more
TL;DR: Overexpression of a transmembrane aspartic protease, termed BACE (for beta-site APP-cleaving enzyme) increased the amount of beta-secretase cleavage products, and these were cleaved exactly and only at known beta- secretase positions.
Journal ArticleDOI
Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease
Denise Harold,Richard Abraham,Paul Hollingworth,Rebecca Sims,Amy Gerrish,Marian L. Hamshere,Jaspreet Singh Pahwa,Valentina Moskvina,Kimberley Dowzell,Amy L. Williams,Nicola L. Jones,Charlene Thomas,Alexandra Stretton,Angharad R. Morgan,Simon Lovestone,John Powell,Petroula Proitsi,Michelle K. Lupton,Carol Brayne,David C. Rubinsztein,Michael Gill,Brian A. Lawlor,Aoibhinn Lynch,Kevin Morgan,Kristelle Brown,Peter Passmore,David Craig,Bernadette McGuinness,Stephen Todd,Clive Holmes,David M. A. Mann,A. David Smith,Seth Love,Patrick G. Kehoe,John Hardy,Simon Mead,Nick C. Fox,Martin N. Rossor,John Collinge,Wolfgang Maier,Frank Jessen,Britta Schürmann,Hendrik van den Bussche,Isabella Heuser,Johannes Kornhuber,Jens Wiltfang,Martin Dichgans,Lutz Frölich,Harald Hampel,Harald Hampel,Michael Hüll,Dan Rujescu,Alison Goate,John S. K. Kauwe,Carlos Cruchaga,Petra Nowotny,John C. Morris,Kevin Mayo,Kristel Sleegers,Karolien Bettens,Sebastiaan Engelborghs,Peter Paul De Deyn,Christine Van Broeckhoven,Gill Livingston,Nicholas Bass,Hugh Gurling,Andrew McQuillin,Rhian Gwilliam,Panagiotis Deloukas,Ammar Al-Chalabi,Christopher Shaw,Magda Tsolaki,Andrew B. Singleton,Rita Guerreiro,Thomas W. Mühleisen,Markus M. Nöthen,Susanne Moebus,Karl-Heinz Jöckel,Norman Klopp,H-Erich Wichmann,Minerva M. Carrasquillo,V. Shane Pankratz,Steven G. Younkin,Peter Holmans,Michael Conlon O'Donovan,Michael John Owen,Julie Williams +86 more
TL;DR: A two-stage genome-wide association study of Alzheimer's disease involving over 16,000 individuals, the most powerful AD GWAS to date, produced compelling evidence for association with Alzheimer's Disease in the combined dataset.
Journal ArticleDOI
Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity.
Michael S. Wolfe,Michael S. Wolfe,Weiming Xia,Beth L. Ostaszewski,Thekla S. Diehl,W. Taylor Kimberly,Dennis J. Selkoe +6 more
TL;DR: The results indicate that the two transmembrane aspartate residues are critical for both presenilin-1 endoproteolysis and γ-secretase activity, and suggest that presenILin 1 is either a unique diaspartyl cofactor for ιsecretase or is itselfγ- secretase, an autoactivated intramembranous aspartyl protease.
Journal ArticleDOI
Intracellular amyloid-β in Alzheimer's disease
TL;DR: Although the classical view is that Aβ is deposited extracellularly, emerging evidence from transgenic mice and human patients indicates that this peptide can also accumulate intraneuronally, which may contribute to disease progression.
References
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Journal ArticleDOI
The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
Jie Kang,H. G. Lemaire,A. Unterbeck,J. M. Salbaum,Colin L. Masters,K.-H. Grzeschik,Gerd Multhaup,Konrad Beyreuther,Benno Müller-Hill +8 more
TL;DR: An apparently full-length complementary DNA clone coding for the A4 polypeptide is isolated and sequenced and suggests that the cerebral amyloid deposited in Alzheimer's disease and aged Down's syndrome is caused by aberrant catabolism of a cell-surface receptor.
Journal ArticleDOI
Amyloid β-peptide is produced by cultured cells during normal metabolism
Christian Haass,Michael G. Schlossmacher,Michael G. Schlossmacher,Albert Y. Hung,Carmen Vigo-Pelfrey,A Mellon,Beth L. Ostaszewski,Ivan Lieberburg,Edward H. Koo,Dale B. Schenk,David B. Teplow +10 more
TL;DR: The unexpected identification of the 4K (Mr 4,000) Aβ and a truncated form of Aβ in media from cultures of primary cells and untransfected and β-APP-transfected cell lines grown under normal conditions provide the basis for using simple cell culture systems to identify drugs that block the formation or release of A β, the primary protein constituent of the senile plaques of Alzheimer's disease.
Journal ArticleDOI
Production of the Alzheimer amyloid β protein by normal proteolytic processing
Mikio Shoji,Todd E. Golde,Jorge Ghiso,Tobun T. Cheung,Steven Estus,Lillian M. Shaffer,Xiao Dan Cai,Deborah M. McKay,Ron Tintner,B. Frangione,Steven G. Younkin +10 more
TL;DR: Human mononuclear leukemic cells expressing a beta AP-bearing, carboxyl-terminal beta APP derivative released significant amounts of a soluble 4-kilodalton beta AP derivative essentially identical to the beta AP deposited in Alzheimer's disease.
Journal ArticleDOI
Cleavage of amyloid beta peptide during constitutive processing of its precursor
Frederick Esch,Pamela S. Keim,Eric C. Beattie,Russell W. Blacher,Alan R. Culwell,Tilman Oltersdorf,Donald McClure,Pamela J. Ward +7 more
TL;DR: Direct protein structural analyses showed that constitutive processing in human embryonic kidney 293 cells cleaves APP in the interior of the A Beta P, thus preventing A beta P deposition.
Journal ArticleDOI
Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein
Andreas Weidemann,G. König,D. Bunke,Peter Fischer,J. Michael Salbaum,Colin L. Masters,Konrad Beyreuther +6 more
TL;DR: To study the putative precursor proteins of Alzheimer's disease A4 amyloid protein, polyclonal and monoclonal antibodies were raised against a recombinant bacterial PreA4(695) fusion protein to identify the precursors in different cell lines as well as in human brain homogenates and cerebrospinal fluid.
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