Mitochondrial Complex I as a Pathologic and Therapeutic Target for Parkinson’s Disease
Kamatham Pushpa Tryphena, Uppala Sai Nikhil, Poojitha Pinjala, Saurabh Srivastava, Shashi Bala Singh, Dharmendra Kumar Khatri
Abstract
The prevalence of Parkinson's disease (PD) continues to increase despite substantial research. Mounting evidence states that dysfunctional mitochondrial bioenergetics play a vital role in PD etiology. A disturbance in the electron transport chain, more precisely, disruption of the mitochondrial complex I (MCI), is the most detrimental factor. Due to increased susceptibility toward MCI damage, the dopaminergic neurons experience oxidative stress and a compromise in ATP production, leading to neurodegeneration and PD. This article reviews the association of MCI with pathological mechanisms like α-synucleinopathy, neuroinflammation, oxidative stress, and ER stress and also describes the potential therapeutic options explored to overcome MCI dysfunction and related consequences.