RT Journal Article
T1 Disruption of mitochondrial complex I induces progressive parkinsonism.
A1 Gonzalez-Rodriguez, Patricia
A1 Zampese, Enrico
A1 Stout, Kristen A
A1 Guzman, Jaime N
A1 Ilijic, Ema
A1 Yang, Ben
A1 Tkatch, Tatiana
A1 Stavarache, Mihaela A
A1 Wokosin, David L
A1 Gao, Lin
A1 Kaplitt, Michael G
A1 Lopez-Barneo, Jose
A1 Schumacker, Paul T
A1 Surmeier, D James
K1 Animals
K1 Dendrites
K1 Dopamine
K1 Female
K1 Mice
K1 Parkinsonian Disorders
K1 Substantia Nigra
AB Loss of functional mitochondrial complex I (MCI) in the dopaminergic neurons of the substantia nigra is a hallmark of Parkinson's disease1. Yet, whether this change contributes to Parkinson's disease pathogenesis is unclear2. 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 paradigm3,4.
PB Nature Publishing Group
YR 2021
FD 2021-11-03
LK https://hdl.handle.net/10668/27577
UL https://hdl.handle.net/10668/27577
LA en
NO González-Rodríguez P, Zampese E, Stout KA, Guzman JN, Ilijic E, Yang B, et al. Disruption of mitochondrial complex I induces progressive parkinsonism. Nature. 2021 Nov;599(7886):650-656.
DS RISalud
RD Apr 17, 2025