Document Detail

Piperidine acetic acid based γ-secretase modulators directly bind to Presenilin-1.
MedLine Citation:
PMID:  22229075     Owner:  NLM     Status:  Publisher    
Aβ42 is believed to play a causative role in Alzheimer's disease (AD) pathogenesis. γ-Secretase modulators (GSMs) are actively being pursued as potential AD therapeutics because they selectively alter the cleavage site of the amyloid precursor protein (APP) to reduce the formation of Aβ42. However, the binding partner of acid based GSMs was unresolved until now. We have developed clickable photoaffinity probes based on piperidine acetic acid GSM-1 and identified PS1 as the target within the γ-secretase complex. Furthermore, we provide evidence that allosteric interaction of GSMs with PS1 results in a conformational change in the active site of the γ-secretase complex leading to the observed modulation of γ-secretase activity.
Christina J Crump; Benjamin A Fish; Suita V Castro; De-Ming Chau; Natalya Gertsik; Kwangwook Ahn; Cory Stiff; Nikolay Pozdnyakov; Kelly R Bales; Douglas S Johnson; Yue-Ming Li
Related Documents :
20951965 - Structure-function analysis of the human jc polyomavirus establishes the lstc pentasacc...
21463585 - The calponin regulatory region is intrinsically unstructured: novel insight into actin-...
1703135 - Effect of monoclonal antibodies to epstein-barr virus envelope glycoproteins on epstein...
2072445 - An amino-terminal fragment of the friend murine leukemia virus envelope glycoprotein bi...
12106415 - Effect of temperature and calcium on the binding properties of the ampa receptor in fro...
25147485 - Large scale affinity calculations of cyclodextrin host-guest complexes: understanding t...
Publication Detail:
Journal Detail:
Title:  ACS chemical neuroscience     Volume:  2     ISSN:  1948-7193     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2012-1-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101525337     Medline TA:  ACS Chem Neurosci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  705-710     Citation Subset:  -    
Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Grant Support
R01 NS076117-01//NINDS NIH HHS

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Tuning the Surface Structure and Optical Properties of CdSe Clusters Using Coordination Chemistry.
Next Document:  Novel Modeling Approach to Generate a Polymeric Nanofiber Scaffold for Salivary Gland Cells.