scholarly journals RNA Interference-mediated Silencing of X11α and X11β Attenuates Amyloid β-Protein Levels via Differential Effects on β-Amyloid Precursor Protein Processing

2005 ◽  
Vol 280 (15) ◽  
pp. 15413-15421 ◽  
Author(s):  
Zhongcong Xie ◽  
Donna M. Romano ◽  
Rudolph E. Tanzi
Keyword(s):  
Rna Interference ◽  
Amyloid Precursor Protein ◽  
Amyloid Β ◽  
Protein Processing ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Processing ◽  
Amyloid Β Protein ◽  
Protein Levels ◽  
Β Protein ◽  
Β Amyloid

scholarly journals Loss of Function ofATXN1Increases Amyloid β-Protein Levels by Potentiating β-Secretase Processing of β-Amyloid Precursor Protein

2010 ◽  
Vol 285 (12) ◽  
pp. 8515-8526 ◽  
Author(s):  
Can Zhang ◽  
Andrew Browne ◽  
Daniel Child ◽  
Jason R. DiVito ◽  
Jesse A. Stevenson ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Amyloid Β ◽  
Precursor Protein ◽  
Amyloid Β Protein ◽  
Loss Of Function ◽  
Protein Levels ◽  
Β Protein ◽  
Β Amyloid

scholarly journals Potential Link between Amyloid β-Protein 42 and C-terminal Fragment γ 49–99 of β-Amyloid Precursor Protein

2003 ◽  
Vol 278 (27) ◽  
pp. 24294-24301 ◽  
Author(s):  
Toru Sato ◽  
Naoshi Dohmae ◽  
Yue Qi ◽  
Nobuto Kakuda ◽  
Hiroaki Misonou ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Amyloid Β ◽  
Precursor Protein ◽  
Amyloid Β Protein ◽  
Terminal Fragment ◽  
Β Protein ◽  
Potential Link ◽  
Β Amyloid

Presenilin 1 Regulates the Processing of β-Amyloid Precursor Protein C-Terminal Fragments and the Generation of Amyloid β-Protein in Endoplasmic Reticulum and Golgi†

Biochemistry ◽  
1998 ◽  
Vol 37 (47) ◽  
pp. 16465-16471 ◽  
Author(s):  
Weiming Xia ◽  
Jimin Zhang ◽  
Beth L. Ostaszewski ◽  
William Taylor Kimberly ◽  
Peter Seubert ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Amyloid Precursor Protein ◽  
Protein C ◽  
Amyloid Β ◽  
Precursor Protein ◽  
Presenilin 1 ◽  
Amyloid Β Protein ◽  
Β Protein ◽  
Β Amyloid

scholarly journals RNA Interference Silencing of the Adaptor Molecules ShcC and Fe65 Differentially Affect Amyloid Precursor Protein Processing and Aβ Generation

2006 ◽  
Vol 282 (7) ◽  
pp. 4318-4325 ◽  
Author(s):  
Zhongcong Xie ◽  
Yuanlin Dong ◽  
Uta Maeda ◽  
Weiming Xia ◽  
Rudolph E. Tanzi
Keyword(s):  
Rna Interference ◽  
Amyloid Precursor Protein ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Adaptor Proteins ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Processing ◽  
Amyloid Β Protein ◽  
App Processing ◽  
Rnai Silencing

The amyloid precursor protein (APP) and its pathogenic by-product amyloid-β protein (Aβ) play central roles in Alzheimer disease (AD) neuropathogenesis. APP can be cleaved by β-secretase (BACE) and α-secretase to produce APP-C99 and APP-C83. These C-terminal fragments can then be cleaved by γ-secretase to produce Aβ and p3, respectively. p3 has been reported to promote apoptosis, and Aβ is the key component of senile plaques in AD brain. APP adaptor proteins with phosphotyrosine-binding domains, including ShcA (SHC1), ShcC (SHC3), and Fe65 (APBB1), can bind to and interact with the conserved YENPTY motif in the APP-C terminus. Here we have described for the first time the effects of RNA interference (RNAi) silencing of ShcA, ShcC, and Fe65 expression on APP processing and Aβ production. RNAi silencing of ShcC led to reductions in the levels of APP-C-terminal fragments (APP-CTFs) and Aβ in H4 human neuroglioma cells stably overexpressing full-length APP (H4-FL-APP cells) but not in those expressing APP-C99 (H4-APP-C99 cells). RNAi silencing of ShcC also led to reductions in BACE levels in H4-FL-APP cells. In contrast, RNAi silencing of the homologue ShcA had no effect on APP processing or Aβ levels. RNAi silencing of Fe65 increased APP-CTF levels, although also decreasing Aβ levels in H4-FL-APP cells. These findings suggest that pharmacologically blocking interaction of APP with ShcC and Fe65 may provide novel therapeutic strategies against AD.

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