Modulation of Gamma-Secretase for the Treatment of Alzheimer's Disease
Joint Authors
Austin, Wesley F.
Bronk, Brian S.
McKee, Timothy D.
Hubbs, Jed L.
Ives, Jeff
Loureiro, Robyn M. B.
Jonker, Jeff
Fuller, Nathan O.
Dumin, Jo Ann
Xia, Weiming
Shen, Ruichao
Tate, Barbara
Pojasek, Kevin
Source
International Journal of Alzheimer's Disease
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-12-19
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
The Amyloid Hypothesis states that the cascade of events associated with Alzheimer's disease (AD)—formation of amyloid plaques, neurofibrillary tangles, synaptic loss, neurodegeneration, and cognitive decline—are triggered by Aβ peptide dysregulation (Kakuda et al., 2006, Sato et al., 2003, Qi-Takahara et al., 2005).
Since γ-secretase is critical for Aβ production, many in the biopharmaceutical community focused on γ-secretase as a target for therapeutic approaches for Alzheimer's disease.
However, pharmacological approaches to control γ-secretase activity are challenging because the enzyme has multiple, physiologically critical protein substrates.
To lower amyloidogenic Aβ peptides without affecting other γ-secretase substrates, the epsilon (ε) cleavage that is essential for the activity of many substrates must be preserved.
Small molecule modulators of γ-secretase activity have been discovered that spare the ε cleavage of APP and other substrates while decreasing the production of Aβ42.
Multiple chemical classes of γ-secretase modulators have been identified which differ in the pattern of Aβ peptides produced.
Ideally, modulators will allow the ε cleavage of all substrates while shifting APP cleavage from Aβ42 and other highly amyloidogenic Aβ peptides to shorter and less neurotoxic forms of the peptides without altering the total Aβ pool.
Here, we compare chemically distinct modulators for effects on APP processing and in vivo activity.
American Psychological Association (APA)
Tate, Barbara& McKee, Timothy D.& Loureiro, Robyn M. B.& Dumin, Jo Ann& Xia, Weiming& Pojasek, Kevin…[et al.]. 2012. Modulation of Gamma-Secretase for the Treatment of Alzheimer's Disease. International Journal of Alzheimer's Disease،Vol. 2012, no. 2012, pp.1-10.
https://search.emarefa.net/detail/BIM-454868
Modern Language Association (MLA)
Tate, Barbara…[et al.]. Modulation of Gamma-Secretase for the Treatment of Alzheimer's Disease. International Journal of Alzheimer's Disease No. 2012 (2012), pp.1-10.
https://search.emarefa.net/detail/BIM-454868
American Medical Association (AMA)
Tate, Barbara& McKee, Timothy D.& Loureiro, Robyn M. B.& Dumin, Jo Ann& Xia, Weiming& Pojasek, Kevin…[et al.]. Modulation of Gamma-Secretase for the Treatment of Alzheimer's Disease. International Journal of Alzheimer's Disease. 2012. Vol. 2012, no. 2012, pp.1-10.
https://search.emarefa.net/detail/BIM-454868
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-454868