title: Back to the future with phenotypic screening.
abstract: 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.
authors.affiliation: Cellular Neurobiology Laboratory, The Salk Institute for Biological Studies , La Jolla, California 92037-1002, United States.
authors.forename: Marguerite
authors.initials: M
authors.lastname: Prior
authors.forename: Chandramouli
authors.initials: C
authors.lastname: Chiruta
authors.forename: Antonio
authors.initials: A
authors.lastname: Currais
authors.forename: Josh
authors.initials: J
authors.lastname: Goldberg
authors.forename: Justin
authors.initials: J
authors.lastname: Ramsey
authors.forename: Richard
authors.initials: R
authors.lastname: Dargusch
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Maher
authors.forename: David
authors.initials: D
authors.lastname: Schubert
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology; D010641:Phenotype
chemical_list: D018696:Neuroprotective Agents