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 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 mitochondria! 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.