Fibrillar α-synuclein toxicity depends on functional lysosomes
نویسندگان
چکیده
منابع مشابه
Induction of CNS α-synuclein pathology by fibrillar and non-amyloidogenic recombinant α-synuclein
BACKGROUND α-Synuclein (αS) is the major component of several types of brain inclusions including Lewy bodies, a hallmark of Parkinson's disease. Aberrant aggregation of αS also is associated with cellular demise in multiple neurologic disorders collectively referred to as synucleinopathies. Recent studies demonstrate the induction of αS pathology by a single intracerebral injection of exogenou...
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Posttranslational modification of proteins by attachment of small ubiquitin-related modifier (SUMO) contributes to numerous cellular phenomena. Sumoylation sometimes creates and abolishes binding interfaces, but increasing evidence points to another role for sumoylation in promoting the solubility of aggregation-prone proteins. Using purified α-synuclein, an aggregation-prone protein implicated...
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Aggregation and neuron-to-neuron transmission are attributes of α-synuclein relevant to its pathogenetic role in human synucleinopathies such as Parkinson's disease. Intraparenchymal injections of fibrillar α-synuclein trigger widespread propagation of amyloidogenic protein species via mechanisms that require expression of endogenous α-synuclein and, possibly, its structural corruption by misfo...
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The aggregation of α-synuclein (αSyn) is a neuropathologic hallmark of Parkinson's disease and other synucleinopathies. In Lewy bodies, αSyn is extensively phosphorylated, predominantly at serine 129 (S129). Recent studies in yeast have shown that, at toxic levels, αSyn disrupts Rab homeostasis, causing an initial endoplasmic reticulum-to-Golgi block that precedes a generalized trafficking coll...
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The mechanism by which the Parkinson's disease-related protein alpha-synuclein (alpha-syn) causes neurodegeneration has not been elucidated. To determine the genes that protect cells from alpha-syn, we used a genetic screen to identify suppressors of the super sensitivity of the yeast Saccharomyces cerevisiae expressing alpha-syn to killing by hydrogen peroxide. Forty genes in ubiquitin-depende...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2020
ISSN: 0021-9258
DOI: 10.1074/jbc.ra120.013428