The Mechanism and Function of Glia in Parkinson's Disease

Abstract

Parkinson's disease (PD) is a neurodegenerative disease that primarily affects elderly people. The mechanism on onset and progression of PD is unknown. Currently, there are no effective treatment strategies for PD. PD is thought to be the loss of midbrain dopaminergic neurons, but it has recently been discovered that glia also affects brain tissue homeostasis, defense, and repair in PD. The neurodegenerative process is linked to both losses of glial supportive-defensive functions and toxic gain of glial functions. In this article, we reviewed the roles of microglia, astrocytes, and oligodendrocytes in the development of PD, as well as the potential use of glia-related medications in PD treatment.

Keywords: Parkinson's disease; alpha-synuclein; astrocytes; microglia; oligodendrocytes.

Figure 1

Microglia in Parkinson's disease. In Parkinson's disease, debris containing α-syn and DAMPs from neurons activates microglia through regulating Fyn, Kv1.3, and P2Y₁₂R via ROCK and p38 MAPK pathways. The α-syn induces neuroinflammatory response through activating TLR4/TLR9/TLR2, NLRP3 inflammasome, ARRB1/ARRB2/STAT1/NF-κB/NLPR3, and LRRK2/NFAT pathways. The phagocytized α-syn impairs the autophagy through PELI1, TLR4/p62/SQSTM1, and p38/TFEB/NLRP3 pathways.

Figure 2

Astrocytes in Parkinson's disease. The engulfed α-syn has a variety of effects on astrocytes. The α-syn induces MHC-II expression in astrocytes and activates T cells. The α-syn induces the release Ca2+-dependent glutamate and activates eNMDARs to accelerate the injury and loss of synapsis. Drd2 inhibits the activation of NLRP3 by regulating β-arrestin2.

Figure 3

Interaction of glia and neurons in Parkinson's disease. Neurons secrete α-syn to extracellular matrix which induces glia reaction differently. The molecules are transmitted among neurons and glia to form a complex regulating network. Astrocytes are induced to A1s by microglia through inflammatory factors IL-6, TNF-α, and C1q. Astrocytes are converted into functional neurons by ASCL1, LMX1A, NEUROD1, and NeAL218 transcription programs. Cx32 and FABP7 regulate the oligodendrocytes survival.