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1. Amyloid beta-protein assembly as a therapeutic target of Alzheimer's disease........................................... 1 
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Amyloid beta-protein assembly as a therapeutic target of Alzheimer's disease. 
Author: Yamin, Ghiam 1 ; Ono, Kenjiro; Inayathullah, Mohammed; Teplow, David B 1 Department of Neurology, 
David Geffen School of Medicine at UCLA, 635 Charles E. Young Drive South (Room 445), Los Angeles, 
California 90095, USA. 


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Abstract: Alzheimer's disease (AD), the most common neurodegenerative disorder in the aged, is characterized 
by the cerebral deposition of fibrils formed by the amyloid beta-protein (Abeta), a 40-42 amino acid peptide. The 
folding of Abeta into neurotoxic oligomeric, protofibrillar, and fibrillar assemblies is hypothesized to be the key 
pathologic event in AD. Abeta is formed through cleavage of the Abeta precursor protein by two 
endoproteinases, beta-secretase and gamma-secretase, that cleave the Abeta N-terminus and C-terminus, 
respectively. These facts support the relevance of therapeutic strategies targeting Abeta production, assembly, 
clearance, and neurotoxicity. Currently, no disease-modifying therapeutic agents are available for AD patients. 
Instead, existing therapeutics provide only modest symptomatic benefits for a limited time. We summarize here 
recent efforts to produce therapeutic drugs targeting Abeta assembly. A number of approaches are being used 
in these efforts, including immunological, nutraceutical, and more classical medicinal chemical (peptidic 
inhibitors, carbohydrate-containing compounds, polyamines, "drug-like" compounds, chaperones, metal 
chelators, and osmolytes), and many of these have progressed to phase III clinical trails. We also discuss briefly 
a number of less mature, but intriguing, strategies that have therapeutic potential. Although initial trials of some 
disease-modifying agents have failed, we argue that substantial cause for optimism exists. 


Links: UC-eLinks, UC-eLinks, UC-eLinks 
Subject: Index Medicus; 
MeSH: Animals, Clinical Trials as Topic, Humans, Immunotherapy, Plant Preparations -- therapeutic use, 


Protein Folding, Small Molecule Libraries -- therapeutic use, Alzheimer Disease -- drug therapy (major), 
Alzheimer Disease -- immunology, Alzheimer Disease -- metabolism, Amyloid beta-Peptides -- metabolism 
(major), Drug Design (major) 


Substance: Substance: Amyloid beta-Peptides; CAS: 0; Substance: Plant Preparations; CAS: 0; Substance: 
Small Molecule Libraries; CAS: 0; 
Correspondence author: Yamin, Ghiam 
Publication title: Current pharmaceutical design 


Journal abbreviation: Curr. Pharm. Des. 
Grant: AG027818. United States. 
AT004511. United States. 


Volume: 14 
Issue: 30 
Pages: 3231-3246 
Number of pages: 16 
Publication year: 2008 
Year: 2008 


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eISSN: 1873-4286 
Source type: Scholarly Journals 
Peer reviewed: Yes 
Format availability: Internet 
Language of publication: English 
Document type: Research Support, Non-u.s. Gov't, Research Support, N.i.h., Extramural, Journal Article, 

Review 
Publication history : 
Accepted date: 09 Feb 2009 
Revised date: 15 Jun 2015; 

First submitted date: 16 Dec 2008 

Update: 2015-06-17 

Accession number: 19075703 

ProQuest document ID: 69893314 

Document URL: http://search.proquest.com/docview/69893314?accountid=14512 

Last updated: 2015-06-17 

Database: Environmental Sciences and Pollution Management 

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