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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2011-1-5
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pubmed:abstractText |
The paradoxical appearance of aggregated ?-synuclein (?syn) in naive transplanted embryonic stem cells in Parkinson's disease (PD) brains has recently been reported, highlighting the possibility of neuron to neuron transmission of ?syn in PD. Here, we demonstrate in a cellular model the presence of ?syn oligomers in the extracellular space, their uptake by neurons, retrograde axonal transport to cell soma, and detrimental effects on neighboring cells. Moreover, we demonstrate that Hsp70 chaperones ?syn in the extracellular space and reduces extracellular ?syn oligomer formation and related toxicity. These novel findings provide evidence that extracellular ?syn oligomers may represent a crucial player in the propagation of pathology in PD, with their modulation by Hsp70 representing a potential new target for therapeutic interventions.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1530-6860
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
326-36
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pubmed:meshHeading |
pubmed-meshheading:20876215-Animals,
pubmed-meshheading:20876215-Axons,
pubmed-meshheading:20876215-Benzoquinones,
pubmed-meshheading:20876215-Cell Line, Tumor,
pubmed-meshheading:20876215-Cell Survival,
pubmed-meshheading:20876215-Cells, Cultured,
pubmed-meshheading:20876215-Coculture Techniques,
pubmed-meshheading:20876215-Culture Media, Conditioned,
pubmed-meshheading:20876215-Dependovirus,
pubmed-meshheading:20876215-Extracellular Space,
pubmed-meshheading:20876215-Genetic Vectors,
pubmed-meshheading:20876215-Green Fluorescent Proteins,
pubmed-meshheading:20876215-HEK293 Cells,
pubmed-meshheading:20876215-HSP70 Heat-Shock Proteins,
pubmed-meshheading:20876215-Humans,
pubmed-meshheading:20876215-Lactams, Macrocyclic,
pubmed-meshheading:20876215-Luciferases,
pubmed-meshheading:20876215-Mice,
pubmed-meshheading:20876215-Neurons,
pubmed-meshheading:20876215-Protein Multimerization,
pubmed-meshheading:20876215-Synaptic Transmission,
pubmed-meshheading:20876215-Transfection,
pubmed-meshheading:20876215-alpha-Synuclein
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pubmed:year |
2011
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pubmed:articleTitle |
Heat-shock protein 70 modulates toxic extracellular ?-synuclein oligomers and rescues trans-synaptic toxicity.
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pubmed:affiliation |
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, 114 16th St., Charlestown, MA 02129, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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