TY - JOUR T1 - Novel insights in the pathophysiology of α-synuclein dysregulation on D2 receptor activity contributing to the vulnerability of dopamine neurons JF - bioRxiv DO - 10.1101/2021.03.30.437775 SP - 2021.03.30.437775 AU - Abeer Dagra AU - Douglas R. Miller AU - Fatemeh Shaerzadeh AU - Min Lin AU - Adithya Gopinath AU - Sharonda Harris AU - Zachary A. Sorrentino AU - Sophia Velasco AU - Adetola R Alonge AU - Janelle Azar AU - Joe J Lebowitz AU - Brittany Ulm AU - Anthea-Mengfei Bu AU - Carissa A. Hansen AU - Nikhil Urs AU - Benoit I. Giasson AU - Habibeh Khoshbouei Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/03/30/2021.03.30.437775.abstract N2 - Pathophysiological damages and loss of function of dopamine neurons precedes their demise and contributes to the early phases of Parkinson’s disease. The presence of aberrant intercellular pathological inclusions of the protein α-synuclein within ventral midbrain dopaminergic neurons is one of the cardinal features of Parkinson’s disease. We employed multiple complementary approaches in molecular biology, electrophysiology, and live-cell imaging to investigate how excessive α-synuclein levels alters multiple characteristics of dopaminergic neuronal dynamics and dopamine transmission prior to neuronal demise. These studies demonstrate that α-synuclein dysregulation of D2 receptor autoinhibition contributes to the vulnerability of dopaminergic neurons, and that modulation thereof can ameliorate the resulting pathophysiology. These novel findings provide mechanistic insights in the insidious loss of dopaminergic function and neurons that characterize Parkinson’s disease progression with significant therapeutic implications.Competing Interest StatementThe authors have declared no competing interest. ER -