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Microglial Phagocytosis and Its Regulation: A Therapeutic Target in Parkinson's Disease?
Elzbieta Janda1, Laura Boi2, Anna R Carta2
1Department of Health Sciences, Magna Graecia University, Catanzaro, Italy.
Abstract:
The role of phagocytosis in the neuroprotective function of microglia has been appreciated for a long time, but only more recently a dysregulation of this process has been recognized in Parkinson's disease (PD). Indeed, microglia play several critical roles in central nervous system (CNS), such as clearance of dying neurons and pathogens as well as immunomodulation, and to fulfill these complex tasks they engage distinct phenotypes. Regulation of phenotypic plasticity and phagocytosis in microglia can be impaired by defects in molecular machinery regulating critical homeostatic mechanisms, including autophagy. Here, we briefly summarize current knowledge on molecular mechanisms of microglia phagocytosis, and the neuro-pathological role of microglia in PD. Then we focus more in detail on the possible functional role of microglial phagocytosis in the pathogenesis and progression of PD. Evidence in support of either a beneficial or deleterious role of phagocytosis in dopaminergic degeneration is reported. Altered expression of target-recognizing receptors and lysosomal receptor CD68, as well as the emerging determinant role of α-synuclein (α-SYN) in phagocytic function is discussed. We finally discuss the rationale to consider phagocytic processes as a therapeutic target to prevent or slow down dopaminergic degeneration.
Insights
Microglia phagocytosis, crucial for brain health, is dysregulated in Parkinson's disease (PD). This review explores its dual role in PD pathogenesis and potential as a therapeutic target for neuroprotection.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are key immune cells in the central nervous system (CNS), performing vital functions like clearing cellular debris and modulating immune responses.
- Phagocytosis, a critical microglial function, is increasingly recognized as dysregulated in Parkinson's disease (PD), impacting neuronal health.
- Defects in microglial phagocytosis and phenotypic plasticity, potentially linked to autophagy, are implicated in neurodegenerative processes.
Purpose of the Study:
- To review the molecular mechanisms of microglial phagocytosis.
- To elucidate the neuro-pathological role of microglia in Parkinson's disease.
- To analyze the functional impact of microglial phagocytosis on PD pathogenesis and progression, considering both beneficial and detrimental effects.
Main Methods:
- Literature review summarizing current knowledge on microglial phagocytosis.
- Analysis of molecular mechanisms underlying microglial function in the CNS.
- Discussion of evidence regarding the role of phagocytosis in dopaminergic degeneration in PD.
Main Results:
- Microglial phagocytosis plays a complex, dual role in Parkinson's disease, potentially being both neuroprotective and neurotoxic.
- Altered expression of receptors involved in target recognition and lysosomal function (e.g., CD68) is observed in PD.
- Alpha-synuclein (α-SYN) emerges as a significant factor influencing microglial phagocytic function in the context of PD.
Conclusions:
- Microglial phagocytosis is a critical process implicated in the pathogenesis and progression of Parkinson's disease.
- Understanding the intricate role of phagocytosis in PD offers potential therapeutic avenues.
- Targeting microglial phagocytic processes presents a promising strategy for developing treatments to slow or prevent dopaminergic neurodegeneration.