geranylgeranylacetone and Parkinsonian-Disorders

Thioredoxin (TRX) is a redox-active protein which plays a cytoprotective role against oxidative stress. Geranylgeranylacetone (GGA), used widely as an anti-ulcer drug, has been reported to induce TRX as well as heat shock protein 70 (HSP70) in hepatocytes and other cells. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), causes dopaminergic denervation and Parkinsonism in humans. The 1-methyl-4-phenylpyridinium ion (MPP(+)), an active metabolite of MPTP, induces cell death in a rat pheochromocytoma cell line (PC12 cells). We found that MPP(+) suppresses TRX expression in PC12 cells. Overexpression or administration of TRX attenuates MPP(+)-induced neurotoxicity on PC12 cells. Moreover, GGA induces expression of TRX and HSP70 and attenuates MPP(+)-induced toxicity in PC12 cells. These results indicate that TRX and GGA have a possible potential as new therapeutic agents for Parkinson disease.

Topics: 1-Methyl-4-phenylpyridinium; Animals; Anti-Ulcer Agents; Cell Survival; Diterpenes; Dose-Response Relationship, Drug; Drug Interactions; HSP70 Heat-Shock Proteins; L-Lactate Dehydrogenase; Neurons; Neurotoxins; Oxidative Stress; Parkinsonian Disorders; PC12 Cells; Rats; Thioredoxins