α-synuclein and p53 functional interplay in physiopathological contexts

Parkinson's disease (PD) is the most frequent agerelated movement disorder due to the loss of dopaminergic neurons.It is characterized at the histological level by the presence of intracellular lesions named Lewy bodies and cell death stigmata.The main constituent of Lewy bodies is α-synuclein (α-syn), a phosphoprotein that is strongly linked to the etiology of both genetic and sporadic PD. α-syn is a protein contributing to dopaminergic neuronal health and numerous evidences indicate that, in physiological conditions α-syn is neuroprotective while, in PD-related pathological conditions, it becomes aggregated and thereby, neurotoxic [1 , 2].More than ten years ago, we were first to show that wild-type α-syn displayed antiapoptotic properties (OMIM entry 163890) and that this function was abolished by its aggregation [3,4].We showed that α-syn overexpression in telencephalon mouse neurons led to decreased cell death via the down-regulation of the tumor suppressor p53 (a key transcription factor involved in apoptosis regulation in neurodegenerative disorders [5,6]) at both protein and transcriptional levels and that this phenotype was abolished by the pro-oxidant neurotoxin and PD-