Caspase inhibition protects nigral neurons against 6-OHDA-induced retrograde degeneration

6-HYDROXYDOPAMINE (6-OHDA) administered intrastriatally to adult rats in a single injection causes neurodegeneration of the nigrostriatal pathway and loss of >50% of dopamine neurons in substantia nigra pars compacta 30 days after administration. The death of nigral neurons occurs, at least partiall y, by a caspase-mediated mechanism. The nigral loss of dopaminergic neurons could be prevented by stereotaxical administration of zVAD.fmk, a caspase inhibitor, into the substantia nigra, indicating that 6-OHDA-induced nigros triatal degeneration involves caspase activation. These results suggest tha t caspases are probably involved in neurodegenerative chronic processes suc h as Parkinson's disease and might be considered as possible targets in the treatment of such neurological disorders. (C) 1999 Lippincott Williams & W ilkins.