Glial phagocytic clearance in Parkinson’s disease

• Published in: Molecular neurodegeneration Vol. 14; no. 1; pp. 16 - 14
• Main Authors: Tremblay, Marie-Eve, Cookson, Mark R., Civiero, Laura
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 05.04.2019; BioMed Central; BMC
• Subjects: Apoptosis; Astrocytes; Astrocytes - metabolism; Brain; Chemokines; Cytokines; Disease; Genetic diversity; Glial cells; Humans; Kinases; Microglia; Microglia - metabolism; Molecular modelling; Movement disorders; Mutation; Nervous system; Neurodegeneration; Neurodegenerative diseases; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - pathology; Neuroglia - metabolism; Neuronal-glial interactions; Neurons; Parkinson Disease - metabolism; Parkinson's disease; Pathogenesis; Pathology; Phagocytes; Phagocytosis; Phagocytosis - physiology; Physiology; Proteins; Reactive astrocytes; Reactive microglia; Review; Synapses; Synapses - metabolism; Target recognition; Reactive microglia; Parkinson’s disease; Phagocytosis; Reactive astrocytes
• ISSN: 1750-1326; 1750-1326
• DOI: 10.1186/s13024-019-0314-8

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.