[HT-01] α-Synuclein and beyond: Find out the true culprit causing neurodegeneration in Parkinson's disease!

[HT-01-4] Molecular mechanisms of selective neuronal vulnerability in PD and &alpha-synuclein

James D. Surmeier (Feinberg School of Medicine Northwestern University, USA)

α-Synuclein is a primary component of Lewy bodies, and mutations / overexpression of it cause Parkinson’s disease (PD). Besides, Braak and colleagues identified Lewy pathologies, namely α-synuclein deposition, in various regions of human brains, and demonstrated the temporal sequence of α-synuclein pathologies that emerge in the brains of PD. However, the relationship between α-synuclein deposition and neuronal dysfunction / neuronal death and underlying mechanisms connecting them are still unclear. Is α-synuclein a true culprit of neurodegeneration in PD? If so, what are the precise molecular mechanisms involved with the neurotoxicity of α-synuclein? What other factors contribute to neurodegeneration in PD? Now it is high time that we should know the details molecular mechanisms involved with neurodegeneration in PD. Does α-Synuclein itself cause neurodegeneration or need other factors, namely α-synuclein and beyond?

Dr. D. James Surmeier is the Nathan Smith Davis Professor and Chair of the Department of Physiology at the Feinberg School of Medicine at Northwestern University. Dr. Surmeier received his Ph.D. in Physiology and Biophysics from the University of Washington. He trained with leaders in the field of neurophysiology, including Dr. Arnold Towe, Dr. William Willis, and Dr. Stephen Kitai. He assumed his current position as Chair of the Department of Physiology at Northwestern University in 2001. Using an array of cutting-edge approaches, Dr. Surmeier’s research program focuses on physiological determinants of Parkinson’s and Huntington’s diseases.

His work has uncovered basic mechanisms underlying neural activity in the basal ganglia and how it is perturbed in these disease states. His work has identified the molecular determinants of network dysfunction in both diseases, paving the way for novel pharmacological and genetic therapies. His pursuit of the mechanisms underlying selective neuronal vulnerability in Parkinson’s disease has led to the identification of activity-dependent calcium entry through Cav1 Ca2+ channels as a primary trigger for mitochondrial oxidant stress in at-risk neurons, providing a potential explanation for the selective vulnerability of substantia nigra dopaminergic neurons -neurons whose loss underlies the cardinal motor symptoms of Parkinson’s disease.