Target-based selection of flavonoids for neurodegenerative disorders

Habitual consumption of dietary flavonoids known to improve mitochondrial bioenergetics and inhibit various secondary sources of reactive oxygen species (ROS) reduces the risk for neurodegenerative disorders such as Parkinson's disease (PD), stroke, and Alzheimer's disease (AD). Combining...

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Bibliographic Details
Published in:Trends in pharmacological sciences (Regular ed.) 2012-11, Vol.33 (11), p.602-610
Main Authors: Jones, Quinton R.D, Warford, Jordan, Rupasinghe, H.P. Vasantha, Robertson, George S
Format: Article
Language:English
Subjects:
Advanced Basic Science
Alzheimer Disease - drug therapy
Animals
Cisplatin - toxicity
Flavonoids - chemistry
Flavonoids - pharmacokinetics
Flavonoids - pharmacology
Flavonoids - therapeutic use
Humans
Mitochondria - metabolism
Parkinson Disease - drug therapy
Reactive Oxygen Species - antagonists & inhibitors
Reactive Oxygen Species - metabolism
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Summary:Habitual consumption of dietary flavonoids known to improve mitochondrial bioenergetics and inhibit various secondary sources of reactive oxygen species (ROS) reduces the risk for neurodegenerative disorders such as Parkinson's disease (PD), stroke, and Alzheimer's disease (AD). Combining specific dietary flavonoids selected on the basis of oral bioavailability, brain penetration, and the inhibition of multiple processes responsible for excessive ROS production may be a viable approach for the prevention and treatment of neurodegenerative disorders. Inclusion of flavonoids that raise cAMP levels in the brain may be of additional benefit by reducing the production of proinflammatory mediators and stimulating the transcriptional machinery necessary for mitochondrial biosynthesis. Preclinical models suggest that flavonoids reduce hearing loss resulting from treatment with the chemotherapeutic drug cisplatin by opposing the excessive production of ROS and proinflammatory mediators implicated in PD, stroke, and AD. Flavonoid combinations optimized for efficacy in models of cisplatin-induced hearing loss (CIHL) may therefore have therapeutic utility for neurodegenerative disorders.
ISSN:0165-6147
1873-3735
DOI:10.1016/j.tips.2012.08.002