Title : Impact of XBP1-mediated PINK1 transcriptional regulation to mitophagy control in parkinson’s disease
Abstract:
Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons and the presence of intracellular inclusions, named Lewy bodies that are mainly composed of misfolded proteins. The accumulation of misfolded proteins is a molecular trigger of a cellular stress response in the endoplasmic reticulum (ER) called the Unfolded Protein Response (UPR). The modulation of the UPR has been demonstrated in post mortem studies of brain samples of patients affected by PD. Interestingly, PINK1 functionally interacts with several genes responsible for sporadic and genetic forms of PD, including PARKIN. PARKIN controls a key transcription factor of the UPR response, XBP1-S ("X-box binding protein 1-Spliced"). PARKIN also regulates the transcription of PINK1. This leads us to postulate that XBP1-S could be involved in the transcriptional regulation of PINK1, which would explain both the decrease in PINK1 mRNA and the failure of the mitophagic response in sporadic forms of PD.
Audience Take Away Notes:
- The audience will learn about a new mechanism implicated in the regulation of a key Parkinson’s disease causative gene PINK1 and the impact of this regulation to ER stress control and PD development.
