Roles of VGLUT2 and Dopamine/Glutamate Co-Transmission in Selective Vulnerability to Dopamine Neurodegeneration.

Autor:	Buck SA; Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States.; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States., Erickson-Oberg MQ; Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States.; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States., Bhatte SH; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States., McKellar CD; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States., Ramanathan VP; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States., Rubin SA; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States., Freyberg Z; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States.; Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States.
Jazyk:	angličtina
Zdroj:	ACS chemical neuroscience [ACS Chem Neurosci] 2022 Jan 19; Vol. 13 (2), pp. 187-193. Date of Electronic Publication: 2022 Jan 07.
DOI:	10.1021/acschemneuro.1c00741
Abstrakt:	Growing evidence has established that a subset of dopamine (DA) neurons co-release glutamate and express vesicular glutamate transporter 2 (VGLUT2). VGLUT2 expression in DA neurons plays a key role in selective vulnerability to DA neurodegeneration in Parkinson's disease (PD). In this review, we summarize recent findings on impacts of VGLUT2 expression and glutamate co-release from DA neurons on selective DA neuron vulnerability. We present evidence that DA neuron VGLUT2 expression may be neuroprotective, boosting DA neuron resilience in the context of ongoing neurodegenerative processes in PD. We highlight genetic and pesticide models of PD that have provided mechanistic insights into selective DA neuron vulnerability. Finally, we discuss potential neuroprotective mechanisms, focusing on roles of VGLUT2 and glutamate in promoting mitochondrial health and diminishing oxidative stress and excitotoxicity. Elucidating these mechanisms may ultimately lead to more effective treatments to boost DA neuron resilience that can slow or even prevent DA neurodegeneration.
Databáze:	MEDLINE
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