Mitochondrial Complex I as a Pathologic and Therapeutic Target for Parkinson’s Disease

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.

Neuroprotective potential of Mentha piperita extract prevents motor dysfunctions in mouse model of Parkinson’s disease through anti-oxidant capacities

“…Repeated exposure of rotenone to rodents induces PD-like motor dysfunctions (bradykinesia, gait alterations and motor coordination deficits) by degeneration of DA producing neurons [37]. It inhibits the mitochondrial complex I of electron transport chain (ETC) and hence elevating oxidative stress leading to PD etiology [38]. Our study harnessed the rotenone-mediated PD motor deficits in mice and observed the therapeutic potential of extract from medicinal…”

“…Repeated exposure of rotenone to rodents induces PD-like motor dysfunctions (bradykinesia, gait alterations and motor coordination deficits) by degeneration of DA producing neurons [ 37 ]. It inhibits the mitochondrial complex I of electron transport chain (ETC) and hence elevating oxidative stress leading to PD etiology [ 38 ]. Our study harnessed the rotenone-mediated PD motor deficits in mice and observed the therapeutic potential of extract from medicinal herb, Mentha piperita through behavioral assays, antioxidant capacities of brain homogenates, extent of neurodegeneration, brain dopamine level determination and expression modulation studies of candidate genes for antioxidant status and synaptogenic activities.…”

Sexually dimorphic mechanisms of VGLUT-mediated protection from dopaminergic neurodegeneration

“…This generates ROS that boosts oxidative stress, causing mitochondrial dysfunction and ultimately DA neuron loss 41 . Critically, mitochondrial ROS-mediated stress is a key aspect of PD pathogenesis 51,52 . We therefore hypothesized that dVGLUT mediates DA neuron resilience by moderating mitochondrial oxidative stress in response to paraquat.…”

β-Synuclein Intermediates α-Synuclein Neurotoxicity in Parkinson’s Disease

“…This insufficiency may result in excessive accumulation of free radicals, disrupting the balance and potentially contributing to the development of PD . MC I of the mitochondrial respiratory chain plays a pivotal role, and its diminished activity is strongly associated with PD. − ion of MC I leads to an increase in reactive ROS production, causing respiratory failure and OS . Furthermore, partial ion of MC I exacerbates the situation by enhancing the mitochondria’s capacity to generate ROS, thereby creating a detrimental feedback loop …”