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.

Common and Rare Variants in TMEM175 Gene Concur to the Pathogenesis of Parkinson’s Disease in Italian Patients

“…Indeed, previous positron emission tomography (PET)/magnetic resonance imaging (MRI) studies have already largely investigated the relationship between neuroinflammation and gray matter alterations in Alzheimer’s disease [ 29 – 31 ]. However, more recently a negative correlation between an increased microglia activation and gray matter volume reduction has been demonstrated also in alpha-synucleinopathies such as PD [ 32 ]. Accordingly, in vitro evidences have suggested that neuronal release of aggregated alpha-synuclein in the central nervous system may activate microglia with production of proinflammatory mediators increasing the rate of neurodegeneration [ 32 ].…”

“…However, more recently a negative correlation between an increased microglia activation and gray matter volume reduction has been demonstrated also in alpha-synucleinopathies such as PD [ 32 ]. Accordingly, in vitro evidences have suggested that neuronal release of aggregated alpha-synuclein in the central nervous system may activate microglia with production of proinflammatory mediators increasing the rate of neurodegeneration [ 32 ].…”

Linking Immune Activation and Parkinson’s Disease

“…PD is influenced by many factors including a mix of immunogenetics and the environment, such as infection history. In recent years, increasing evidence suggests an association with autoimmune conditions, with the involvement of the immune system or its aberrant responses in patients and various experimental models [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. In this special issue, our authors highlight the latest research breakthroughs on the links between immune activation and neuroinflammation and PD, and discuss the challenges and novel therapeutic strategies targeting the immune system ISSN 1877-7171/$35.00 © 2022 -IOS Press.…”

“…Activated microglia can present autoantigens to T cells through MHC class I and II molecules, thereby activating the adaptive immune system. They have also been demonstrated to play a role in the conversion of astrocytes into neurotoxic phenotypes [11].…”

“…In summary, multiple independent studies in clinical and pre-clinical models have provided corroborative evidence of the involvement of central and peripheral immune and inflammatory processes in PD [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Our knowledge of how the immune system contributes to PD pathogenesis is constantly evolving with increasing evidence for a role of several genes and susceptibility loci [1,2].…”