α-Synuclein and Glia in Parkinson's Disease: A Beneficial or a Detrimental Duet for the Endo-Lysosomal System?

α-Synuclein and Glia in Parkinson's Disease: A Beneficial or a Detrimental Duet for the Endo-Lysosomal System? Cell Mol Neurobiol. 2019 Jan 14;: Authors: Filippini A, Gennarelli M, Russo I Abstract Accumulation of α-synuclein (α-syn) species in dopaminergic neurons is one of the main hallmarks of Parkinson's disease (PD). Several factors have been associated with α-syn aggregation process, including an impairment of the proper protein degradation, which might drive the neurons toward an alternative and/or additional clearance mechanism that involves the release of undigested material from the cell. It has been reported that extracellular α-syn, released by stressed and/or degenerating neurons, might widely contribute to the neuronal toxicity and degeneration. Therefore, the uptake and clearance of misfolded/aggregated proteins is a key process to control extracellular deposition of α-syn aggregates, the spreading and progression of the disease. All the main brain cell types, neurons, astrocytes and microglia are able to internalize and degrade extracellular α-syn, however, glial cells appear to be the most efficient scavengers. Accumulating evidence indicates that the endocytosis of α-syn species might be conformation-sensitive, cell- and receptor-type specific, making the scenario highly complex. In this review, we will shed light on the different endocytosis mechanisms and receptors recruited for the uptake and clearance of...
Source: Cellular and Molecular Neurobiology - Category: Cytology Authors: Tags: Cell Mol Neurobiol Source Type: research