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The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.

Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1

Open access
Guzman, Jaime N., Sanchez-Padilla, Javier, Wokosin, David, Kondapalli, Jyothisri, Ilijic, Ema, Schumacker, Paul T., Surmeier, D. James·2010·Nature

Abstract

Parkinson’s disease is a pervasive, ageing-related neurodegenerative disease the cardinal motor symptoms of which reflect the loss of a small group of neurons, the dopaminergic neurons in the substantia nigra pars compacta (SNc). Mitochondrial oxidant stress is widely viewed as being responsible for this loss, but why these particular neurons should be stressed is a mystery. Here we show, using transgenic mice that expressed a redox-sensitive variant of green fluorescent protein targeted to the mitochondrial matrix, that the engagement of plasma membrane L-type calcium channels during normal autonomous pacemaking created an oxidant stress that was specific to vulnerable SNc dopaminergic neurons. The oxidant stress engaged defences that induced transient, mild mitochondrial depolarization or uncoupling. The mild uncoupling was not affected by deletion of cyclophilin D, which is a component of the permeability transition pore, but was attenuated by genipin and purine nucleotides, which are antagonists of cloned uncoupling proteins. Knocking out DJ-1 (also known as PARK7 in humans and Park7 in mice), which is a gene associated with an early-onset form of Parkinson’s disease, downregulated the expression of two uncoupling proteins (UCP4 (SLC25A27) and UCP5 (SLC25A14)), compromised calcium-induced uncoupling and increased oxidation of matrix proteins specifically in SNc dopaminergic neurons. Because drugs approved for human use can antagonize calcium entry through L-type channels, these results point to a novel neuroprotective strategy for both idiopathic and familial forms of Parkinson’s disease.

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Metadata

Authors
Guzman, J. N., Sanchez-Padilla, J., Wokosin, D., Kondapalli, J., Ilijic, E., Schumacker, P. T., & Surmeier, D. J.
Venue
Nature
Published
2010-11-10
Volume
468
Issue
7324
Pages
696-700
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2168126136
Cited by
843
References
16
FWCI
31.43
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. https://app.cochat.ai/papers/10.1038/nature09536
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Guzman, J. N., Sanchez-Padilla, J., Wokosin, D., Kondapalli, J., Ilijic, E., Schumacker, P. T., & Surmeier, D. J. (2010). Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. Nature. https://doi.org/10.1038/nature09536

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