Microglia in Parkinson's Disease

Abstract

Microglia are the primary resident immune cells of the central nervous system. Neuropathological reports have identified augmented microglial activation in brains of patients with neurodegenerative disorders including Parkinson's disease (PD). Extensive research over the years has strengthened the current view on microglia as a player in the pathogenesis of PD and other α-synucleinopathies. In this review, we summarize key findings of the recent three years on microglia in PD with specific relevance to understanding its heterogeneity, dual nature, and specific interactions with pathological α-synuclein strains to mediate its clearance and spreading. This review provides evidence on the relevance of microglia as a putative biomarker and therapeutic target in PD and related disorders.

Keywords: Alpha-synuclein; PET; Parkinson’s disease; biomarker; disease modifying therapy; microglia; multiple system atrophy; neuroinflammatory.

Fig. 1

Annual number of publications until the end of 2021 recorded in PubMed and identified with the search “Microglia” and “Parkinson’s disease”.

Fig. 2

The unresolved heterogeneity of microglia and DAMs in Parkinson’s disease. α-synuclein (α-syn) oligomers as well as pro-inflammatory signals released from the degenerating neuron may trigger activation of microglia in a disease-specific mode (DAMs). Importantly different α-syn polymorphs may induce different microglial responses. Microglia may get different morphological patterns of activation as well as execute different functions: i) the left lower panel shows pro-inflammatory signaling in microglia triggered by α-syn oligomers involving different membrane receptors, NLRP3 inflammasome activation, mitochondrial and oxidative stress, as well as release of toxic pro-inflammatory cytokines; ii). The right lower panel demonstrates a microglial cell which is involved in the uptake and clearance of α-syn either from the extracellular space or through putative nanotubes within the microglial network. Created with BioRender.com.