RT Journal Article
SR Electronic
T1 Novel insights in the pathophysiology of α-synuclein dysregulation on D2 receptor activity contributing to the vulnerability of dopamine neurons
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.30.437775
DO 10.1101/2021.03.30.437775
A1 Abeer Dagra
A1 Douglas R. Miller
A1 Fatemeh Shaerzadeh
A1 Min Lin
A1 Adithya Gopinath
A1 Sharonda Harris
A1 Zachary A. Sorrentino
A1 Sophia Velasco
A1 Adetola R Alonge
A1 Janelle Azar
A1 Joe J Lebowitz
A1 Brittany Ulm
A1 Anthea-Mengfei Bu
A1 Carissa A. Hansen
A1 Nikhil Urs
A1 Benoit I. Giasson
A1 Habibeh Khoshbouei
YR 2021
UL http://biorxiv.org/content/early/2021/03/30/2021.03.30.437775.abstract
AB 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.