Potential targets of microglia in the treatment of neurodegenerative diseases: Mechanism and therapeutic implications.

Abstract

For diverse neurodegenerative disorders, microglial cells are activated. Furthermore, dysfunctional and hyperactivated microglia initiate mitochondrial autophagy, oxidative stress, and pathological protein accumulation, ending with neuroinflammation that exacerbates damage to dopaminergic neurons and contributes significantly to the pathology of neurodegenerative disorder. Microglial over-activation is closely associated with the secretion of pro-inflammatory cytokines, the phagocytosis of injured neurons, and the modulation of neurotoxic environments. This review summarizes the role of microglia neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, cortical degeneration, Lewy body dementia, and Huntington's disease. It also discusses novel forms of cell death such as ferroptosis, cuproptosis, disulfidptosis, and parthanatos (poly(adenosine diphosphate ribose) polymerase 1-dependent cell death), as well as the impact of regulatory factors related to microglial inflammation on microglial activation and neuroinflammation. The aim is to identify potential targets for microglial cell therapy in neurodegenerative diseases.