Endogenous neuroprotection in chronic neurodegenerative disorders: with particular regard to the kynurenines

• Introduction • The role of mitochondrial impairment and oxidative stress in neurodegeneration ‐ Background ‐ Parkinson’s disease ‐ Huntington’s disease • Glutamate excitotoxicity in neurodegeneration ‐ Background ‐ Parkinson’s disease ‐ Huntington’s disease • The kynurenine pathway ‐ Historical overview ‐ The biosynthesis of neuroactive kynurenines ‐ Neuroactive kynurenines: sites of action • Neuroactive kynurenines in neurodegenerative disorders ‐ Parkinson’s disease ‐ Huntington’s disease • Endogenous neuroprotection in Parkinson’s and Huntington’s diseases ‐ Background ‐ L‐carnitine ‐ L‐carnosine ‐ Coenzyme Q10 ‐ Creatine ‐ Cysteamine/cystamine ‐ Eicosapentaenoic acid ‐ α‐lipoic acid ‐ Pyruvate ‐ Taurine ‐ Tocopherol ‐ L‐KYN/KYNA • Concluding remarks Parkinson’s disease (PD) and Huntington’s disease (HD) are progressive chronic neurodegenerative disorders that are accompanied by a considerable impairment of the motor functions. PD may develop for familial or sporadic reasons, whereas HD is based on a definite genetic mutation. Nevertheless, the pathological processes involve oxidative stress and glutamate excitotoxicity in both cases. A number of metabolic routes are affected in these disorders. The decrease in antioxidant capacity and alterations in the kynurenine pathway, the main pathway of the tryptophan metabolism, are features that deserve particular interest, because the changes in levels of neuroactive kynurenine pathway compounds appear to be strongly related to the oxidative stress and glutamate excitotoxicity involved in the disease pathogenesis. Increase of the antioxidant capacity and pharmacological manipulation of the kynurenine pathway are therefore promising therapeutic targets in these devastating disorders.