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Review
. 2020 Oct:144:105028.
doi: 10.1016/j.nbd.2020.105028. Epub 2020 Jul 28.

Microglia and astrocyte dysfunction in parkinson's disease

Tae-In Kam  1 , Jared T Hinkle  2 , Ted M Dawson  3 , Valina L Dawson  4
Affiliations
Review

Microglia and astrocyte dysfunction in parkinson's disease

Tae-In Kam et al. Neurobiol Dis. 2020 Oct.

Abstract

While glia are essential for regulating the homeostasis in the normal brain, their dysfunction contributes to neurodegeneration in many brain diseases, including Parkinson's disease (PD). Recent studies have identified that PD-associated genes are expressed in glial cells as well as neurons and have crucial roles in microglia and astrocytes. Here, we discuss the role of microglia and astrocytes dysfunction in relation to PD-linked mutations and their implications in PD pathogenesis. A better understanding of microglia and astrocyte functions in PD may provide insights into neurodegeneration and novel therapeutic approaches for PD.

Keywords: Astrocyte; Glia; Microglia; Neurodegeneration; Neurodegenerative disease; Neuroinflammation; Parkinson's disease.

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Conflict of interest statement

Declaration of Competing Interest T.M.D. and V.L.D. are founders of and hold shares of stock options and equity in Neuraly, Inc., and they are inventors of some of the technology discussed in this article, which Neuraly, Inc. has licensed from Johns Hopkins University. T.M.D. and V.L.D. are founders of, and are interim Chief Scientific Officer and Chief Executive Officer of, respectively, hold equity in, serve on the Board of Directors of, and are compensated for their roles as consultants to Valted Seq Inc. T.M.D. and V.L.D. are founders of Valted, LLC and hold an ownership equity interest in the company and the value of patents owned by Valted, LLC could be affected by this article. T.M.D. and V.L.D. are consultants to Inhibikase Therapeutics and own stock options in the company. T.M.D. is a paid consultant to Sun Pharmaceutical Industries Ltd.

Figures

Figure 1.
Figure 1.. Neuroinflammation in Parkinson’s Disease
Pathologic α-Synuclein (α-Syn) is released from neurons and transmitted to and activates microglia and astrocytes. PD-associated GBA or LRRK2 mutations impair lysosomal protein degradation, which causes accumulation of α-syn. This leads to oxidative stress and proinflammatory responses. Mutations in Parkin, PINK1 and DJ-1 contribute to enhanced oxidative stress and proinflammatory responses in microglia and astrocytes. This culminates in the release of proinflammatory mediators derived from activated microglia, astrocytes or both, or unknown toxins released from reactive astrocytes that promote dopaminergic neuronal degeneration in PD.
See this image and copyright information in PMC

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