Accession Number : ADA490036


Title :   Using High Throughput Screens to Identify Lead Compounds for Alzheimer's Disease Therapeutics


Descriptive Note : Doctoral thesis


Corporate Author : PRINCETON UNIV NJ


Personal Author(s) : Chen, Jermont


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a490036.pdf


Report Date : Nov 2008


Pagination or Media Count : 140


Abstract : Alzheimer's disease (AD) is the leading cause for dementia affecting over 4.6 million people in the United States. The current FDA approved drugs only provide temporary relief from memory loss symptoms, without treating the underlying root cause of the disease. The amyloid cascade hypothesis suggests that aggregation of the amyloid beta (AB) peptide into a neurotoxic oligiomer initiates the disease. Small molecule compounds have been reported to inhibit AB peptide aggregation, as well as rescue AB induced toxicity. Screens to identify compounds are necessary to increase the chance of developing a therapeutic that prevents AB aggregation and the associated disease. Chapter 1 reviews the possible mechanism for Alzheimer's disease and discusses methods to prevent the disease. Chapter 2 presents results from an E coli based GFP fusion anti-aggregation screen. A library of 65,000 compounds was screened, and potential hits were characterized for aggregation inhibition as well as for the ability to rescue toxicity of the AB peptide Improvements to the screen are also discussed. Chapter 3 presents the results from a screen designed to identify compounds that bind to the AB peptide. Small molecule microarrays (SMM) were used to identify compounds that bind to AB. Compounds that bind have the potential of becoming aggregation inhibitors. Over 20,000 compounds were screened, and several hits from the screen are shown to rescue AB induced toxicity.


Descriptors :   *LEAD COMPOUNDS , *THERAPY , *ALZHEIMER DISEASE , TOXICITY , RESCUES , SIGNS AND SYMPTOMS , THESES , ESCHERICHIA COLI , MEMORY DEVICES , DRUGS , INHIBITION , MENTAL DISORDERS , PEPTIDES , MOLECULES , UNITED STATES , SKILLS


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE