Journal ArticleDOI
Cytosolic amyloid-β peptide 42 escaping from degradation induces cell death
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TLDR
This study ectopically expressed Abeta42 in the cytoplasm of SH-SY5Y neuroblastoma cells by expressing a fusion protein of GFP-tagged ubiquitin and Abeta 42 (GFPUb-Abeta42).About:
This article is published in Biochemical and Biophysical Research Communications.The article was published on 2006-06-02. It has received 17 citations till now. The article focuses on the topics: Cytoplasm & MG132.read more
Citations
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Journal ArticleDOI
Amyloid-like Aggregates Sequester Numerous Metastable Proteins with Essential Cellular Functions
Heidi Olzscha,Sonya M. Schermann,Andreas C. Woerner,Stefan Pinkert,Michael H. Hecht,Gian Gaetano Tartaglia,Michele Vendruscolo,Manajit Hayer-Hartl,F. Ulrich Hartl,R. Martin Vabulas +9 more
TL;DR: It is suggested that amyloidogenic aggregation targets a metastable subproteome, thereby causing multifactorial toxicity and, eventually, the collapse of essential cellular functions.
Journal ArticleDOI
Long-term neprilysin gene transfer is associated with reduced levels of intracellular Abeta and behavioral improvement in APP transgenic mice
Brian Spencer,Robert A. Marr,Edward Rockenstein,Leslie Crews,Anthony Adame,Rewati Potkar,Christina Patrick,Fred H. Gage,Inder M. Verma,Eliezer Masliah +9 more
TL;DR: S sustained expression of neprilysin for up to 6 months lowered not only the amyloid plaque load but also reduced the levels of intracellular Aβ immunoreactivity, which was associated with improved behavioral performance in the water maze and ameliorated the dendritic and synaptic pathology in the APP transgenic mice.
Journal ArticleDOI
Alzheimer's Aβ fused to green fluorescent protein induces growth stress and a heat shock response
Jo Caine,Sonia E. Sankovich,Helma Antony,Helma Antony,Lynne J. Waddington,Peter I. Macreadie,J.N. Varghese,Ian Macreadie,Ian Macreadie +8 more
TL;DR: Yeast may be a new tractable model system for the screening for inhibitors of the stress caused by Aβ, showing that Aβ fusions promote stress in cells and supporting the notion that intracellular Aβ is a toxic molecule.
Journal ArticleDOI
Intracellular distribution of amyloid beta peptide and its relationship to the lysosomal system
Lin Zheng,Angel Cedazo-Minguez,Martin Hallbeck,Fredrik Jerhammar,Jan Marcusson,Alexei Terman +5 more
TL;DR: The results indicate that most Aβ is not localized to Golgi-related structures, endosomes, lysosomes secretory vesicles or other organelles, while the suppression of Aβ secretion increases intracellular intra- and extralysosomal Aβ.
Journal ArticleDOI
Reduced amyloid-β degradation in early Alzheimer's disease but not in the APPswePS1dE9 and 3xTg-AD mouse models.
Anita Stargardt,Judith Gillis,Willem Kamphuis,Anne Wiemhoefer,Lieneke Kooijman,Marcel Raspe,Willemien E. Benckhuijsen,Jan W. Drijfhout,Elly M. Hol,Elly M. Hol,Eric Reits +10 more
TL;DR: Intriguingly, the Aβ‐degrading capacity decreases already during the earliest Braak stages of sAD, and this decline correlates with IDE protein levels, but not with mRNA levels, which suggests that decreased IDE levels could contribute to early sAD.
References
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Journal ArticleDOI
The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics
John Hardy,Dennis J. Selkoe +1 more
TL;DR: It has been more than 10 years since it was first proposed that the neurodegeneration in Alzheimer's disease (AD) may be caused by deposition of amyloid β-peptide in plaques in brain tissue and the rest of the disease process is proposed to result from an imbalance between Aβ production and Aβ clearance.
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
Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein
George G. Glenner,Caine W. Wong +1 more
TL;DR: A purified protein derived from the twisted beta-pleated sheet fibrils in cerebrovascular amyloidosis associated with Alzheimer's disease has been isolated and Amino acid sequence analysis and a computer search reveals this protein to have no homology with any protein sequenced thus far.
Book
Impairment of the ubiquitin proteasome system by protein aggregation
TL;DR: It is reported that protein aggregation directly impaired the function of the ubiquitin-proteasome system, suggesting a potential mechanism linking protein aggregation to cellular disregulation and cell death.
Journal ArticleDOI
Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo: evidence for augmentation of a 42-specific γ secretase
Joanna L. Jankowsky,Joanna L. Jankowsky,Daniel J. Fadale,Jeffrey Anderson,Guilian Xu,Victoria Gonzales,Nancy A. Jenkins,Neal G. Copeland,Michael K. Lee,Linda H. Younkin,Steven L. Wagner,Steven G. Younkin,David R. Borchelt +12 more
TL;DR: A direct correlation between the concentration of Aβ42 and the rate of amyloid deposition is demonstrated and suggests that PS1 variants do not simply alter the preferred cleavage site for γ-secretase, but rather that they have more complex effects on the regulation of ιsecretase and its access to substrates.