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Regulator of G‐protein signaling (RGS10) regulates microglial response to chronic inflammatory stimuli and impacts dopaminergic neuron survival.
Author(s) -
Lee Jae Kyung,
McCoy Melissa K,
Harms Ashley S,
Ruhn Kelly A,
Gold Stephen J,
Tansey Malu G
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1072.5
Subject(s) - microglia , neuroinflammation , neuroprotection , dopaminergic , downregulation and upregulation , inflammation , regulator , tumor necrosis factor alpha , dopamine , biology , neuroscience , immunology , biochemistry , gene
Epidemiological studies suggest that chronic use of non‐steroidal anti‐inflammatory drugs (NSAIDs) lowers the incidence of Parkinson's disease (PD) in humans and implicate neuroinflammatory processes in the death of dopamine (DA) neurons. Chronic systemic inflammation in mice deficient for Regulator of G protein signaling‐10 (RGS10), a microglia‐enriched GTPase accelerating protein (GAP) for G alpha subunits that is also expressed in DA neurons, induced degeneration of the nigrostriatal pathway, suggesting a protective role for RGS10. Knockdown of RGS10 alone in the BV2 microglia cell line resulted in upregulation of inflammation‐related genes and overproduction of neurotoxic cytokines, including Tumor Necrosis Factor (TNF) and enhanced the neurotoxic activity of BV2 conditioned media on the dopaminergic cell line MN9D. Importantly, removal of RGS10 in MN9Ds further enhanced their sensitivity to microglia‐derived mediators, including TNF. Given the neuroprotective effects of RGS10 on DA neuron survival, RGS10 emerges as a novel drug target for the treatment of PD.βα