Interestingly, low doses of RESV exert the same benef icial effects as calor ic restr iction in mice.Moreover, SIRT suppresses apoptotic activ ities of FOXO proteinsand promotes neuronal su rvival.RESV functions as an antioxidant and possibly prevents reactive oxygen speciesinduced apoptosis.However, it is reasonable to assume that therapeutic in terven tions that aim to activate or block sirtu ins, depending on the context, will one day become useful in the treatmentof human diseases.Increased nuclear NAD biosynthesis and SIRT activation prevent axonal degeneration.Mammalian SIRT limits replicative life span in response to chronic genotoxic stress.Science. Calorie restriction extends yeast life span by lowering the level of NADH.Sirtuins: the magnificent seven, function, metabolism and longevity.Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons.View publication stats View publication stats The user has requested enhancement of the downloaded file.Combining specic dietary avonoids 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 avonoids that raise cAMP levels in the brain may be of additional benet by reducing the production of Oxytetracycline proinammatory mediators and stimulating the transcriptional machinery necessary for mitochondrial biosynthesis.Preclinical models suggest that avonoids reduce hearing loss resulting from treatment with the chemotherapeutic drug cisplatin by opposing the excessive production of ROS and proinammatory mediators implicated in PD, stroke, and AD.Flavonoid combinations optimized for efcacy in models of cisplatininduced hearing loss may therefore have therapeutic utility for neurodegenerative disorders.ROS in neurodegeneration A common feature of neurodegenerative disorders is extensive evidence of oxidative stress linked to mitochondrial dysfunction. Mutations responsible for familial forms of AD and PD impair the function of proteins that directly regulate mitochondrial activity or give rise to protein aggregates that interfere with the normal activity of mitochondria, resulting in excessive ROS levels. Impairment of mitochondrial function and excessive ROS generation are also implicated in the neurodegenerative events resulting in hearing loss in patients treated with the chemotherapeutic drug cisplatin. Similarly, the mitochondrial toxins MPP and rotenone have been shown to mimic the pattern of dopamine neuron loss in animals observed with PD. Neuroprotective strategies for agingrelated central nervous system disorders may therefore have to target multiple pathological mechanisms to reduce the excessive production of ROS necessary for disease modication.We review here evidence that avonoids inhibit processes responsible for mitochondrial dysfunction, generation of ROS, and the resultant neuroinammation sufciently to oppose neurodegeneration.Based on this assessment, we Honokiol propose optimal avonoid combinations to mitigate that may also be useful in the prevention and treatment of other neurodegenerative disorders.Unfortunately, cisplatin accumulates in the kidney, resulting in nephrotoxicity, ototoxicity, and peripheral neuropathy, respectively.Although active hydration of patients reduces the risk of nephrotoxicity, there are no effective treatments for the prevention of cisplatininduced ototoxicity and neuropathy.Many of the pathological processes implicated in neurodegenerative disorders, such as mitochondrial dysfunction leading to the excessive generation of ROS, calcium and iron overloading, inammation, and apoptosis, are also thought to contribute to cisplatininduced neuropathy and ototoxicity.