The Contribution of Microglia to Neuroinflammation in Parkinson's Disease

Abstract

With the world's population ageing, the incidence of Parkinson's disease (PD) is on the rise. In recent years, inflammatory processes have emerged as prominent contributors to the pathology of PD. There is great evidence that microglia have a significant neuroprotective role, and that impaired and over activated microglial phenotypes are present in brains of PD patients. Thereby, PD progression is potentially driven by a vicious cycle between dying neurons and microglia through the instigation of oxidative stress, mitophagy and autophagy dysfunctions, a-synuclein accumulation, and pro-inflammatory cytokine release. Hence, investigating the involvement of microglia is of great importance for future research and treatment of PD. The purpose of this review is to highlight recent findings concerning the microglia-neuronal interplay in PD with a focus on human postmortem immunohistochemistry and single-cell studies, their relation to animal and iPSC-derived models, newly emerging technologies, and the resulting potential of new anti-inflammatory therapies for PD.

Keywords: Parkinson’s disease; animal models; brain; iPSC; microglia; neurodegeneration; neuroinflammation.

Figure 1

Historical overview of the different model systems used in PD microglia research. Figure created using BioRender.com.

Figure 2

Neuron-microglia cross talk and selected inflammatory pathways involved in PD. (a) Inflammatory loop initiated by neuronal demise and propagated by microglial dysfunction. (b) Inflammatory pathways associated with α-synuclein (i), LRRK2 (ii), parkin (iii) or DJ-1 (iv) in the context of PD pathology. This figure was created with BioRender.com.