Mort neuronale dans les modèles expérimentaux de la maladie de Parkinson

Abstract

A better knowledge of molecular pathways involved in the neuronal cell death occurring in Parkinson's disease is essential to achieve therapeutics able to block the degenerative process. These pathways have been partially elucidated using experimental models created by either 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which are able to mimick the histological (death of dopaminergic nigral neurons) and biochemical (oxidative stress and mitochondrial inhibition) hallmarks of Parkinson's disease. Cell death induced by these neurotoxins is thought to be apoptotic. At the very end-stage, this process depends on activated caspase-3. At earlier stages, in these models, cell death is regulated by p53 and Bcl-2 family proteins but also by the transcriptional factor NF-κB and MAP-kinases. Modulating such regulatory processes may have potential therapeutic benefit for Parkinson's disease.