Recent progress report on DNA B-Z transition modulated by rare earth-amino acid complex and Alzheimer's disease amyloid beta

2010 ◽  
Vol 28 (6) ◽  
pp. 820-823 ◽  
Author(s):  
Jie GENG ◽  
Xiaogang QU
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rare Earth ◽  
Amino Acid ◽  
Amyloid Beta ◽  
Recent Progress ◽  
Progress Report ◽  
Acid Complex ◽  
Amino Acid Complex

scholarly journals The amyloid-beta forming tripeptide cleavage mechanism of γ-secretase

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
David M Bolduc ◽  
Daniel R Montagna ◽  
Matthew C Seghers ◽  
Michael S Wolfe ◽  
Dennis J Selkoe
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amino Acid ◽  
Amyloid Beta ◽  
Aβ Peptides ◽  
Enzyme Substrate ◽  
Disease Mutations ◽  
Initial Substrate ◽  
Binding Pockets ◽  
Amino Acid Binding

γ-secretase is responsible for the proteolysis of amyloid precursor protein (APP) into short, aggregation-prone amyloid-beta (Aβ) peptides, which are centrally implicated in the pathogenesis of Alzheimer’s disease (AD). Despite considerable interest in developing γ-secretase targeting therapeutics for the treatment of AD, the precise mechanism by which γ-secretase produces Aβ has remained elusive. Herein, we demonstrate that γ-secretase catalysis is driven by the stabilization of an enzyme-substrate scission complex via three distinct amino-acid-binding pockets in the enzyme’s active site, providing the mechanism by which γ-secretase preferentially cleaves APP in three amino acid increments. Substrate occupancy of these three pockets occurs after initial substrate binding but precedes catalysis, suggesting a conformational change in substrate may be required for cleavage. We uncover and exploit substrate cleavage preferences dictated by these three pockets to investigate the mechanism by which familial Alzheimer’s disease mutations within APP increase the production of pathogenic Aβ species.

Proteolytic processing of the amyloid-beta protein precursor of Alzheimer's disease

2002 ◽  
Vol 38 ◽  
pp. 37-49 ◽  
Author(s):  
Janelle Nunan ◽  
David H Small
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Alternative Pathway ◽  
Protein A ◽  
Proteolytic Processing ◽  
Gamma Secretase ◽  
Amyloid Beta Protein ◽  
Protein Precursor ◽  
Amyloid Beta Protein Precursor

The proteolytic processing of the amyloid-beta protein precursor plays a key role in the development of Alzheimer's disease. Cleavage of the amyloid-beta protein precursor may occur via two pathways, both of which involve the action of proteases called secretases. One pathway, involving beta- and gamma-secretase, liberates amyloid-beta protein, a protein associated with the neurodegeneration seen in Alzheimer's disease. The alternative pathway, involving alpha-secretase, precludes amyloid-beta protein formation. In this review, we describe the progress that has been made in identifying the secretases and their potential as therapeutic targets in the treatment or prevention of Alzheimer's disease.

Sign in / Sign up

Export Citation Format

Share Document