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Glial Phagocytic Clearance in Parkinson's Disease


Glial Phagocytic Clearance in Parkinson's Disease

Marie-Eve Tremblay et al. Mol Neurodegener.


An emerging picture suggests that glial cells' loss of beneficial roles or gain of toxic functions can contribute to neurodegenerative conditions. Among glial cells, microglia and astrocytes have been shown to play phagocytic roles by engulfing synapses, apoptotic cells, cell debris, and released toxic proteins. As pathogenic protein accumulation is a key feature in Parkinson's disease (PD), compromised phagocytic clearance might participate in PD pathogenesis. In contrast, enhanced, uncontrolled and potentially toxic glial clearance capacity could contribute to synaptic degeneration. Here, we summarize the current knowledge of the molecular mechanisms underlying microglial and astrocytic phagocytosis, focusing on the possible implication of phagocytic dysfunction in neuronal degeneration. Several endo-lysosomal proteins displaying genetic variants in PD are highly expressed by microglia and astrocytes. We also present the evidence that lysosomal defects can affect phagocytic clearance and discuss the therapeutic relevance of restoring or enhancing lysosomal function in PD.

Keywords: Parkinson’s disease; Phagocytosis; Reactive astrocytes; Reactive microglia.

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The Authors declare that they have no competing interests.

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Fig. 1
Fig. 1
Phagocytic pathway in glial cells. Glial cell can recognize and uptake extracellular materials (targets) via specific receptors (receptor-target recognition). Targets are internalized and degraded through the endolysosomal machinery. Several PD-linked proteins intervene in the endolysosomal machinery and are highlighted in red
Fig. 2
Fig. 2
Phagocytic clearance dysfunction in PD neurodegeneration. a Dopaminergic terminals in the striatum are surrounded by astrocytic and microglial processes. b PD is characterized by dopaminergic neuronal death, proteinaceous accumulations positive for α-syn in the surviving neurons as well as in astrocytes, accompanied by extended gliosis and neuroinflammation. Reactive glia can phagocytize neuronal debris and released aggregated α-syn, attenuating neurodegeneration. Multiple factors can cause phagocytic clearance mistargeting or dysfunction (enhance or decrease) thus exacerbating the neurodegenerative process

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