Microglia and Astrocytes Dysfunction and Key Neuroinflammation-Based Biomarkers in Parkinson's Disease

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease, with symptoms such as tremor, bradykinesia with rigidity, and depression appearing in the late stage of life. The key hallmark of PD is the loss or death of dopaminergic neurons in the region substantia nigra pars compacta. Neuroinflammation plays a key role in the etiology of PD, and the contribution of immunity-related events spurred the researchers to identify anti-inflammatory agents for the treatment of PD. Neuroinflammation-based biomarkers have been identified for diagnosing PD, and many cellular and animal models have been used to explain the underlying mechanism; however, the specific cause of neuroinflammation remains uncertain, and more research is underway. So far, microglia and astrocyte dysregulation has been reported in PD. Patients with PD develop neural toxicity, inflammation, and inclusion bodies due to activated microglia and a-synuclein-induced astrocyte conversion into A1 astrocytes. Major phenotypes of PD appear in the late stage of life, so there is a need to identify key early-stage biomarkers for proper management and diagnosis. Studies are under way to identify key neuroinflammation-based biomarkers for early detection of PD. This review uses a constructive analysis approach by studying and analyzing different research studies focused on the role of neuroinflammation in PD. The review summarizes microglia, astrocyte dysfunction, neuroinflammation, and key biomarkers in PD. An approach that incorporates multiple biomarkers could provide more reliable diagnosis of PD.

Keywords: Parkinson’s disease; astrocytes; biomarkers; drug development; glial cells; microglia.

Figure 1

Microglia and microglial receptors in PD. Resting microglia are activated by different stimuli, which ultimately activate MAPK and cell death. Activation of microglia alternatively leads to neuroinflammation and loss of DA neurons and causes PD.

Figure 2

Astrocytes in Parkinson’s disease. Toxic alpha-synuclein convert resting astrocytes into reactive astrocyte, which further disrupts balance of cytokines that can possibly result in loss of DA neurons.