Parkinson’s Disease (PD) is the second most common neurodegenerative disorder seen, especially in the elderly. Tremor, shaking, movement problems, and difficulty with balance and coordination are among the hallmarks, and dopaminergic neuronal loss in substantia nigra pars compacta of the brain and aggregation of intracellular protein α-synuclein are the pathological characterizations. Neuroinflammation has emerged as an involving mechanism at the initiation and development of PD. It is a complex network of interactions comprising immune and non-immune cells in addition to mediators of the immune response. Microglia, the resident macrophages in the CNS, take on the leading role in regulating neuroinflammation and maintaining homeostasis. Under normal physiological conditions, they exist as “homeostatic” but upon pathological stimuli, they switch to the “reactive state”. Pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes are used to classify microglial activity with each phenotype having its own markers and released mediators. When M1 microglia are persistent, they will contribute to various inflammatory diseases, including neurodegenerative diseases, such as PD. In this review, we focus on the role of microglia mediated neuroinflammation in PD and also signaling pathways, receptors, and mediators involved in the process, presenting the studies that associate microglia-mediated inflammation with PD. A better understanding of this complex network and interactions is important in seeking new therapies for PD and possibly other neurodegenerative diseases.

Neuroinflammation in the pathogenesis of neurodegenerative diseases is still a subject of discussion, as it might be either the cause or the result of neurodegeneration. Misfolded or improperly aggregated α-synuclein in Parkinson’s Disease, can cause inflammatory responses, indicating a mechanistic relationship between α-synuclein pathology and neuroinflammation. The aim of this study was to investigate the role of DNA topoisomerase IIβ, the key player of DNA topology, in the neuroinflammation process in an age-dependent transgenic Parkinson’s Disease mouse model overexpressing the A53T mutant α-synuclein. In this study, transgenic and control mice were bred in three age groups as early (3 months), mid (8 months), and late (12 months) disease stages. Behavioral experiments were carried out to compare the age-related cognitive and motor coordination functions. Cytokine levels in the serum and protein expression levels in the dissected brain were analyzed by both western blot and immunofluorescence staining. A decline was observed in the cognitive and motor coordination functions depending on age. Disease-related markers at protein level appeared even in the early stage, and accordingly, a significant increase was observed in inflammatory markers and cytokine levels compared to control. DNA Topoisomerase IIβ and Nurr1 levels decreased in transgenic mice, especially more dramatically in the early stage. The combined effect of reduced Nurr1 and DNA Topoisomerase IIβ, along with increased inflammation, may provide a better understanding of the pathogenesis of Parkinson’s Disease at early-stage and requires for further investigation of the potential alterations in topo IIβ as an intervention strategy for this disease.