Disruption of mitochondrial complex I induces progressive parkinsonism
☆ Watchresearch · published 2021-11-01 · by Gao L, González-Rodríguez P, Guzman JN, Ilijic E, Kaplitt MG, López-Barneo J, Schumacker PT, Stavarache MA, Stout KA, Surmeier DJ, Tkatch T, Wokosin DL, Yang B, Zampese E
Nature · 2021 Nov
Abstract
Loss of functional mitochondrial complex I (MCI) in the dopaminergic neurons of the substantia nigra is a hallmark of Parkinson's disease 1 . Yet, whether this change contributes to Parkinson's disease pathogenesis is unclear 2 . Here we used intersectional genetics to disrupt the function of MCI in mouse dopaminergic neurons. Disruption of MCI induced a Warburg-like shift in metabolism that enabled neuronal survival, but triggered a progressive loss of the dopaminergic phenotype that was first evident in nigrostriatal axons. This axonal deficit was accompanied by motor learning and fine motor deficits, but not by clear levodopa-responsive parkinsonism-which emerged only after the later loss of dopamine release in the substantia nigra. Thus, MCI dysfunction alone is sufficient to cause progressive, human-like parkinsonism in which the loss of nigral dopamine release makes a critical contribution to motor dysfunction, contrary to the current Parkinson's disease paradigm 3,4 .
Ratings (0): Breadth — · Depth — · Enjoyment — · Usefulness —
Neurotransmitters
Stimuli
Community
Log in to rate and share your notes.
No contributions yet.