Apoptosis: its relevance to Parkinson's disease

Although reports on the morphological characteristics of apoptosis in Parkinson's disease remain controversial, accumulating evidence suggests that the molecular and biochemical pathways of apoptosis are involved in dopaminergic cell death in Parkinson's disease and in related cellular and animal models. This evidence includes the activation of the mitogen activated protein (MAP) kinase pathway, the induction of Bax, prostate apoptosis response-4 (Par-4) and glyceraldehyde-3-phosphate dehydrogenase, evidence of aberrant activation of the cell cycle machinery, and the activation of caspases. In cell culture and animal models therapeutic interference with the signalling phase of apoptosis, e.g. inhibition of the MAP kinase pathway, provides morphological and functional protection. In contrast, inhibition of the propagation and execution phase of apoptosis, e.g. by inhibition of caspases, blocks cell death but may result in survival of a dysfunctional neuron. For full functional recovery, the combination of an anti-apoptotic together with a neurorestorative therapy may be necessary. (C) 2001 Elsevier Science B.V. All rights reserved.