scholarly journals Elevation of β-Amyloid Peptide 2–42 in Sporadic and Familial Alzheimer's Disease and Its Generation in PS1 Knockout Cells

2001 ◽  
Vol 276 (46) ◽  
pp. 42645-42657 ◽  
Author(s):  
Jens Wiltfang ◽  
Hermann Esselmann ◽  
Philippe Cupers ◽  
Manuela Neumann ◽  
Hans Kretzschmar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Peptide ◽  
Familial Alzheimer’S Disease ◽  
Β Amyloid ◽  
Familial Alzheimer's Disease ◽  
Β Amyloid Peptide

scholarly journals Syntaxin 5 interacts with presenilin holoproteins, but not with their N- or C-terminal fragments, and affects β-amyloid peptide production

2004 ◽  
Vol 381 (3) ◽  
pp. 619-628 ◽  
Author(s):  
Kei SUGA ◽  
Takami TOMIYAMA ◽  
Hiroshi MORI ◽  
Kimio AKAGAWA
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Full Length ◽  
Precursor Protein ◽  
Amyloid Peptide ◽  
Familial Alzheimer’S Disease ◽  
Aβ Amyloid ◽  
Β Amyloid ◽  
Familial Alzheimer's Disease

Mutations in presenilins 1 and 2 (PS1 and PS2) account for the majority of cases of early-onset familial Alzheimer's disease. However, the trafficking and interaction of PSs with other proteins in the early secretory pathways are poorly understood. Using co-immunoprecipitation, we found that PS bound to Syx5 (syntaxin 5), which is a target-soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor involved in endoplasmic reticulum (ER)–Golgi vesicular transport in vivo. Syx5 interacted only with the full-length PS holoproteins and not with the naturally occurring N- or C-terminal fragments. The PS holoproteins co-immunoprecipitated with the mutant Syx5, which localized to the ER and Golgi compartments, despite the substitution of the transmembrane region with that of syntaxin 1A. In contrast, the transmembrane deletion mutant that localized to the cytosol, but not to the ER or Golgi compartments, did not co-immunoprecipitate the PS holoproteins. The PS1 variant linked to familial Alzheimer's disease (PS1ΔE9), lacking the region that contains the endoproteolytic cleavage site in the cytoplasmic loop, showed markedly decreased binding to Syx5. Immunofluorescence and sucrose-density-gradient fractionation analyses showed that the full-length PS holoproteins co-localized with Syx5 to the ER and cis-Golgi compartments. Furthermore, Syx5 overexpression resulted in the accumulation of PS holoproteins and the β-amyloid precursor protein, and reduced the secretion of the Aβ (amyloid β) peptide in COS-7 cells. In summary, these results indicate that Syx5 binds to full-length PSs and affects the processing and trafficking of β-amyloid precursor protein in the early secretory compartments.

Pentapeptide Amides Interfere with the Aggregation of β-Amyloid Peptide of Alzheimer's Disease

2002 ◽  
Vol 292 (4) ◽  
pp. 931-936 ◽  
Author(s):  
Csaba Hetényi ◽  
Zoltán Szabó ◽  
Éva Klement ◽  
Zsolt Datki ◽  
Tamás Körtvélyesi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Peptide ◽  
Β Amyloid ◽  
Β Amyloid Peptide

scholarly journals Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease

2005 ◽  
Vol 171 (1) ◽  
pp. 87-98 ◽  
Author(s):  
W. Haung Yu ◽  
Ana Maria Cuervo ◽  
Asok Kumar ◽  
Corrinne M. Peterhoff ◽  
Stephen D. Schmidt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Survival ◽  
Mammalian Target Of Rapamycin ◽  
Amyloid Peptide ◽  
Survival Pathways ◽  
Secretase Activity ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Β Amyloid Peptide

Macroautophagy, which is a lysosomal pathway for the turnover of organelles and long-lived proteins, is a key determinant of cell survival and longevity. In this study, we show that neuronal macroautophagy is induced early in Alzheimer's disease (AD) and before β-amyloid (Aβ) deposits extracellularly in the presenilin (PS) 1/Aβ precursor protein (APP) mouse model of β-amyloidosis. Subsequently, autophagosomes and late autophagic vacuoles (AVs) accumulate markedly in dystrophic dendrites, implying an impaired maturation of AVs to lysosomes. Immunolabeling identifies AVs in the brain as a major reservoir of intracellular Aβ. Purified AVs contain APP and β-cleaved APP and are highly enriched in PS1, nicastrin, and PS-dependent γ-secretase activity. Inducing or inhibiting macroautophagy in neuronal and nonneuronal cells by modulating mammalian target of rapamycin kinase elicits parallel changes in AV proliferation and Aβ production. Our results, therefore, link β-amyloidogenic and cell survival pathways through macroautophagy, which is activated and is abnormal in AD.

Strength training or green tea prevent memory deficits in a β-amyloid peptide-mediated Alzheimer's disease model

2021 ◽  
Vol 143 ◽  
pp. 111186
Author(s):  
Helen L. Schimidt ◽  
Guilherme S. Carrazoni ◽  
Alexandre Garcia ◽  
Ivan Izquierdo ◽  
Pâmela B. Mello-Carpes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Strength Training ◽  
Green Tea ◽  
Disease Model ◽  
Memory Deficits ◽  
Amyloid Peptide ◽  
Β Amyloid ◽  
Β Amyloid Peptide

scholarly journals AIP-1 ameliorates β-amyloid peptide toxicity in a Caenorhabditis elegans Alzheimer's disease model

2009 ◽  
Vol 18 (15) ◽  
pp. 2739-2747 ◽  
Author(s):  
Wail M. Hassan ◽  
David A. Merin ◽  
Virginia Fonte ◽  
Christopher D. Link
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Caenorhabditis Elegans ◽  
Disease Model ◽  
Amyloid Peptide ◽  
Β Amyloid ◽  
Β Amyloid Peptide

scholarly journals The Influence of Endoproteolytic Processing of Familial Alzheimer's Disease Presenilin 2 on Aβ42 Amyloid Peptide Formation

1999 ◽  
Vol 274 (49) ◽  
pp. 35233-35239 ◽  
Author(s):  
Helmut Jacobsen ◽  
Dieter Reinhardt ◽  
Manfred Brockhaus ◽  
Daniel Bur ◽  
Christine Kocyba ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Peptide ◽  
Familial Alzheimer’S Disease ◽  
Peptide Formation ◽  
Presenilin 2 ◽  
Familial Alzheimer's Disease
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