INFLUENCE OF R-LIPOIC ACID ON INTRACELLULAR GLUTATHIONE IN HUMAN DOPAMINERGIC NEUROBLASTOMA CELLS: IMPLICATIONS FOR PARKINSON’S DISEASE.

The consistent findings of decreased levels of the major antioxidant glutathione in substantia nigra of patients with idiopathic Parkinson's disease (PD) has provided most of the basis for the oxidative stress hypothesis of the etiology of PD. Oxidative stress and mitochondrial dysfunction signify two important biochemical events associated with the loss of dopaminergic neurons in PD. Studies using in vitro and in vivo PD models and in affected tissues from the disease itself have demonstrated a selective inhibition of mitochondrial complex I activity that appears to affect normal mitochondrial physiology leading to neuronal cell death. R-lipoic acid plays a fundamental role in mitochondrial metabolism as a coenzyme for pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase and as a substrate for the NADPH-dependent enzyme glutathione reductase. To address the question of the possible mechanism of R-lipoic acid-mediated protection, we have investigated its effect on human dopaminergic SH-SY5Y cells exposed to rotenone, a specific complex I inhibitor. We found that rotenone dose- and time- dependently altered SH-SY5Y cell viability associated with a decreased of glutathione (GSH) levels and ATP production. We observed a protective effect R-lipoic acid on SH-SY5Y cells against rotenone indicating that the replenishment of normal GSH levels within the cells may hold an important key to therapeutics for PD. Supported by the University of Bologna, Funds for Selected Research Topics