[Seminar] Natural products and their derivatives for the treatment of age-related neurological disorders
Pamela Maher, Salk Institute for Biological Studies, La Jolla, USA
| When | 08 Sep, 2017 at 04:00 pm |
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| Where | Room 3.02 |
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Seminar
Title: Natural products and their derivatives for the treatment of age-related neurological disorders
Speaker: Pamela Maher
Affiliation: Salk Institute for Biological Studies, La Jolla, USA
Host: Federico Herrera, Cell Structure and Dynamics Lab
Abstract:
There are no drugs that halt the progression of any age-associated neurodegenerative disease. This is likely due to the failure of drug developers to recognize that while there are mutations that predispose individuals to disease as they get older, the vast majority of neurodegenerative diseases arise from a confluence of multiple, toxic insults. Thus, it is unlikely that the current single target approach is going to yield useful drugs for these conditions. The identification of multi-target lead compounds is needed and their selection should be based upon a requirement for their efficacy in phenotypic screening assays that reflect the biology of the aging brain. This approach to neurodegenerative disease drug discovery is likely to produce safe and effective drugs.
Plant secondary metabolites (natural products) are the ideal source of lead compounds because they have evolved to interact at low affinity with multiple enzymes. Indeed, the chemical scaffolds of the majority of drugs in the clinic are based upon those of natural products. My laboratory has completed a series of proof of principle experiments demonstrating that some polyphenolic natural products are exceptionally effective in halting disease progression in a wide variety of animal models of age-associated neurodegenerative disease and ischemia, and that the potency and medicinal chemical properties of these compounds can be dramatically improved without loosing their multi-target activities.
The single target, high affinity drug approach to neurodegenerative disease is unlikely to identify compounds that halt disease progression. Drug discovery paradigms based upon phenotypic screening are more likely to succeed.
