Journal
ACS CHEMICAL NEUROSCIENCE
Volume 5, Issue 7, Pages 503-513Publisher
AMER CHEMICAL SOC
DOI: 10.1021/cn500051h
Keywords
Phenotypic screening; Alzheimer's; neurodegeneration; drug discovery; medicinal chemistry; cell culture; aging
Funding
- National Institutes of Health [NIH-R01-AG035055]
- Burns Foundation
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There are no disease-modifying drugs for any old age associated neurodegenerative disease or stroke. This is at least in part due to the failure of drug developers to recognize that the vast majority of neurodegenerative diseases arise from a confluence of multiple toxic insults that accumulate during normal aging and interact with genetic and environmental risk factors. Thus, it is unlikely that the current single target approach based upon rare dominant mutations or even a few preselected targets is going to yield useful drugs for these conditions. Therefore, the identification of drug candidates for neurodegeneration should be based upon their efficacy in phenotypic screening assays that reflect the biology of the aging brain, not a single, preselected target. It is argued here that this approach to drug discovery is the most likely to produce safe and effective drugs for neurodegenerative diseases.
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