Polyphenolic compounds for treating neurodegenerative disorders involving protein misfolding.
A diverse group of neurodegenerative diseases are characterized by progressive, age-dependent intracellular formation of misfolded protein aggregates. These include Alzheimer's disease, Huntington's disease, Parkinson's disease and a number of tau-mediated disorders. There is no effective treatment for any of these disorders; currently approved interventions are designed to treat disease symptoms and generally lead to modest modulation of clinical symptoms. None are known to mitigate underlying neuropathologic mechanisms and, thus, it is not unexpected that existing treatments appear ineffective in modulating disease progression. We note that these neurodegenerative disorders all share a common mechanistic theme in that depositions of misfolded protein in the brain is a key molecular feature underlying disease onset and/or progression. While previous studies have identified a number of drugs and nutraceuticals capable of interfering with the formation and/or stability of misfolded protein aggregates, none have been demonstrated to be effective in vivo for treating any of the neurodegenerative disorders. We hereby review accumulating evidence that a select nutraceutical grape-seed polyphenolic extract (GSPE) is effective in vitro and in vivo in mitigating certain misfolded protein-mediated neuropathologic and clinical phenotypes. We will also review evidence implicating bioavailability of GSPE components in the brain and the tolerability as well as safety of GSPE in animal models and in humans. Collectively, available information supports continued development of the GSPE for treating a variety of neurodegenerative disorders involving misfolded protein-mediated neuropathologic mechanisms.
Ho
Lap
L
Center of Excellence for Novel Approaches to Neurodiagnostics and Neurotherapeutics, Brain Institute, Center of Excellence for Research in Complementary and Alternative Medicine in Alzheimer's Disease, Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Pasinetti
Giulio Maria
GM
D000818:Animals; D005419:Flavonoids / Q000627:therapeutic use*; D056604:Grape Seed Extract / Q000627:therapeutic use; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D010636:Phenols / Q000627:therapeutic use*; D059808:Polyphenols; D017510:Protein Folding; D057165:Proteostasis Deficiencies / Q000188:drug therapy*
D005419:Flavonoids; D056604:Grape Seed Extract; D010636:Phenols; D059808:Polyphenols