NAIP protects the nigrostriatal dopamine pathway in an intrastriatal 6-OHDA rat model of Parkinson's disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder of the basal ganglia, associated with the inappropriate death of dopaminergic neu rons of the substantia nigra pars compacta (SNc). Here, we show that adenov irally mediated expression of neuronal apoptosis inhibitor protein (NAIP) a meliorates the loss of nigrostriatal function following intrastriatal 6-OHD A administration by attenuating the death of dopamine neurons and dopaminer gic fibres in the striatum. In addition, we also addressed the role of the cysteine protease caspase-3 activity in this adult 6-OHDA model, because a role for caspases has been implicated in the loss of dopamine neurons in PD , and because NAIP is also a reputed inhibitor of caspase-3. Although caspa se-3-like proteolysis was induced in the SNc dopamine neurons of juvenile r ats lesioned with 6-OHDA and in adult rats following axotomy of the medial forebrain bundle, caspase-3 is not induced in the dopamine neurons of adult 6-OHDA-lesioned animals. Taken together, these results suggest that therap eutic strategies based on NAIP may have potential value for the treatment o f PD.