Autophagic failure promotes the exocytosis and intercellular transfer of α-synuclein.
Autophagic failure promotes the exocytosis and intercellular transfer of α-synuclein.
Exp Mol Med. 2013;45:e22
Authors: Lee HJ, Cho ED, Lee KW, Kim JH, Cho SG, Lee SJ
Abstract
The accumulation of abnormal protein aggregates is a major characteristic of many neurodegenerative disorders, including Parkinson's disease (PD). The intracytoplasmic deposition of α-synuclein aggregates and Lewy bodies, often found in PD and other α-synucleinopathies, is thought to be linked to inefficient cellular clearance mechanisms, such as the proteasome and autophagy/lysosome pathways. The accumulation of α-synuclein aggregates in neuronal cytoplasm causes numerous autonomous changes in neurons. However, it can also affect the neighboring cells through transcellular transmission of the aggregates. Indeed, a progressive spreading of Lewy pathology among brain regions has been hypothesized from autopsy studies. We tested whether inhibition of the autophagy/lysosome pathway in α-synuclein-expressing cells would increase the secretion of α-synuclein, subsequently affecting the α-synuclein deposition in and viability of neighboring cells. Our results demonstrated that autophagic inhibition, via both pharmacological and genetic methods, led to increased exocytosis of α-synuclein. In a mixed culture of α-synuclein-expressing donor cells with recipient cells, autophagic inhibition resulted in elevated transcellular α-synuclein transmission. This increase in pro...
Source: exp Mol Med - Category: Molecular Biology Authors: Lee HJ, Cho ED, Lee KW, Kim JH, Cho SG, Lee SJ Tags: Exp Mol Med Source Type: research
More News: Brain | Genetics | Molecular Biology | Neurology | Parkinson's Disease | Pathology | Study