Schematic representation of ICP10PK-mediated neuroprotection from MPP+-induced PCD. ICP10PK activates the PI3-K/Akt pathway through Ras activation, as previously described.13,17 The activated pathway results in up-regulation/stabilization of Bcl-2. This counteracts MPP+-induced calpain I activation and subsequent mobilization of Bax to the mitochondria, AIF release and nuclear translocation, and caspase-3 activation. ICP10PK also causes up-regulation/stabilization of Hsp70, by an as yet unknown mechanism. Arrows represent activation, dotted arrows represent potentially involved factors, while reversed âTâ symbols represent inhibition.