Commitment of 1-methyl-4-phenylpyrinidinium ion-induced neuronal cell death by proteasome-mediated degradation of p35 cyclin-dependent kinase 5 activator.

ABSTRACT: The dysfunction of proteasomes and mitochondria has been implicated in the pathogenesis of Parkinson disease. However, the mechanism by which this dysfunction causes neuronal cell death is unknown. We studied the role of cyclin-dependent kinase 5 (Cdk5)-p35 in the neuronal cell death induced by 1-methyl-4-phenylpyrinidinium ion (MPP+), which has been used as an in vitro model of Parkinson disease. When cultured neurons were treated with 100 microM MPP+, p35 was degraded by proteasomes at 3 h, much earlier than the neurons underwent cell death at 12-24 h. The degradation of p35 was accompanied by the down-regulation of Cdk5 activity. We looked for the primary target of MPP+ that triggered the proteasome-mediated degradation of p35. MPP+ treatment for 3 h induced the fragmentation of the mit

SUBMITTER: Endo R 

PROVIDER: S-EPMC2758003 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature