Regulator of G-protein signaling 10 promotes dopaminergic neuron survival via regulation of the microglial inflammatory response.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Jae-Kyung LeeMalú G Tansey

Abstract

Epidemiological studies suggest that chronic use of nonsteroidal anti-inflammatory drugs lowers the incidence of Parkinson's disease (PD) in humans and implicate neuroinflammatory processes in the death of dopamine (DA) neurons. Here, we demonstrate that regulator of G-protein signaling 10 (RGS10), a microglia-enriched GAP (GTPase accelerating protein) for Galpha subunits, is an important regulator of microglia activation. Flow-cytometric and immunohistochemical analyses indicated that RGS10-deficient mice displayed increased microglial burden in the CNS, and exposure to chronic systemic inflammation induced nigral DA neuron loss measured by unbiased stereology. Primary microglia isolated from brains of RGS10-deficient mice displayed dysregulated inflammation-related gene expression profiles under basal and stimulated conditions in vitro compared with that of primary microglia isolated from wild-type littermates. Similarly, knockdown of RGS10 in the BV2 microglia cell line resulted in dysregulated inflammation-related gene expression, overproduction of tumor necrosis factor (TNF), and enhanced neurotoxic effects of BV2 microglia on the MN9D dopaminergic cell line that could be blocked by addition of the TNF decoy receptor etane...Continue Reading

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Citations

Oct 13, 2009·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Jae-Kyung LeeMalú G Tansey
Oct 1, 2010·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Melinda E Lull, Michelle L Block
Mar 21, 2012·Breast Cancer Research : BCR·Harriet WikmanKlaus Pantel
Aug 19, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jae-Kyung LeeMalú G Tansey
May 24, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Xi ChenMalú G Tansey
Jul 9, 2009·Journal of Visualized Experiments : JoVE·Sandra PennartzAndreas Bosio
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Feb 3, 2016·Journal of Neuroinflammation·Jae-Kyung LeeMalú G Tansey
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Apr 25, 2016·Progress in Neurobiology·Valerie JoersAnna R Carta
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Jul 14, 2020·Bioinformatics·Benjamin DeMeo, Bonnie Berger
Oct 27, 2018·Frontiers in Cellular Neuroscience·Chittappen K PrajeethMartin Stangel
Nov 2, 2019·International Journal of Molecular Sciences·Virginie Bottero, Judith A Potashkin

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