Abid Oueslati
Universit�© Laval School of Medicine, Canada
CHU de Quebec Research Center Quebec, Canada
Scientific Tracks Abstracts: Neurochem Neuropharm
Increasing evidences suggest that phosphorylation at S129 (pS129) may be an important regulator of alpha-synuclein aggregation, Lewy bodies formation and neurotoxicity in Parkinsonâ��s disease (PD) and related synucleinopathies. Recent efforts to probe the relationship between alpha-synuclein phosphorylation and its aggregation and toxicity, using S� E/D or S� A substitutions, to mimic or to block phosphorylation at this residue, respectively, have yielded controversial results. However, our previous in vitro phosphorylation studies demonstrate that the phosphomimics do not reproduce the structural and functional consequences of pS129 and thus may not be suitable for modeling the effect of phosphorylation in vivo. Recently, we reported that members of the Polo like Kinase family, especially PLK2, phosphorylate �±-syn in vitro and in cell culture and in vivo. To validate these findings in vivo and determine whether targeting the PLKs is a viable therapeutic target, we examined the effect of PLK2 overexpression on alpha-synuclein phosphorylation, aggregation and toxicity in a rat model of PD using a recombinant AAV vector-mediated system. The expression and the neuronal localization of each construct were confirmed by immunohistochemistry. The levels of endogenous pS129 were assessed using immunohistochemical and biochemical approaches. The effect of PLK2 overexpression on the dopaminergic neuronal loss was assessed by stereological quantification and the cellular analysis were correlated with the behavioral effect measured by the cylinder test. This approach allowed us to determine the relationship between alpha-synuclein phosphorylation, aggregation and toxicity and provide novel mechanistic insight into the role of phosphorylation in the pathogenesis of PD and therapeutic strategies based on targeting this modification.
Abid Oueslati has completed his PhD in 2008 from University of the Mediterranean-Marseilles, France and then he joined the Swiss Federal Institute of Technology in Lausanne (EPFL), Switzerland for a Post-doctoral training. In 2015, he joined the Department de Molecular Medicine at the Université Laval-School of Medicine as Assistant Professor. His research program is focused on the study of the implication of alpha-synuclein in Parkinson’s disease pathogenesis and treatments.
