Seminários em Neurociência e Cognição: Pathological aggregation of a-Synuclein in Parkinson’s disease and related pathologies and its consequences

17/novembro (sexta-feira), 13-14h, Auditório 5 do Beta e também no https://meet.google.com/jyb-wtvm-hgd

Patrick Pierre Michel - Team Experimental Therapeutics of Parkinson’s disease; Sorbonne Université, Paris Brain Institute ‐ ICM; Inserm, CNRS, APHP, Hôpital de la Pitié Salpêtrière

Título: Pathological aggregation of a-Synuclein in Parkinson’s disease and related pathologies and its consequences

Resumo: Parkinson’s disease (PD) is a common neurodegenerative disorder of aging primarily characterized by a loss of voluntary motor control. Motor control abnormalities result from the progressive loss of midbrain substantia nigra (SN) dopamine (DA) neurons and subsequent nigro-striatal dopaminergic deafferentation. Another major histopathological hallmark of this disorder is the presence of intracellular proteinaceous inclusions called Lewy bodies (LBs) in neuronal somas, and Lewy neurites in neuronal processes. LBs are considered a key marker of neuronal degeneration in PD since they are found at sites particularly predisposed to neuronal loss, the SN and the locus coeruleus. LBs are complex intracellular inclusions enriched with α-Synuclein (αS), a membrane protein whose physiological function is still not fully understood. I will demonstrate in my presentation that it is possible to model pathological aggregation of αS and its deleterious consequences for DA neurons in mouse midbrain cultures chronically exposed to fibril seeds of human recombinant αS. I will also describe how basic knowledge about αS seed amplification is now applied for the diagnosis of PD and related disorders. I will finally show that under certain conditions, αS fibrils have also the potential to seed the aggregation of tau, another aggregation-prone protein involved tauopathies.

Biografia: Patrick Pierre Michel holds a Doctorate in Pharmacy [1985] and a Ph.D. in Neuroscience [1990] from University Claude Bernard (Lyon 1). He worked previously in both academic and pharmaceutical environments. He has solid expertise in cellular pharmacology and developed several cell culture models for investigating mechanisms of neurodegeneration and neuroinflammation. Some of these models are currently applied for phenotypic screening approaches and structure-activity relationship studies in collaboration with medicinal chemists. Although the research work is essentially centered on cell-based assays, animal models have been also implemented in some research studies, generally in complement to the in vitro work. Besides his research work, Patrick Pierre Michel administered a cell culture facility (>200 users), at the Paris Brain Institute [2011-2021]. His current research interests focus on neurodegenerative events involved in Parkinson's disease and related disorders with a particular interest in the role played by amyloid-type protein aggregation, oxidative stress, and inflammatory processes in disease progression. He is the inventor of several patents and the author or co-author of 114 original publications (H index 47).