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J Biol Chem. 2010 Mar 19;285(12):9262-72. doi: 10.1074/jbc.M109.081125. Epub 2010 Jan 13.

Direct transfer of alpha-synuclein from neuron to astroglia causes inflammatory responses in synucleinopathies.

Author information

1
Department of Anatomy, School of Medicine, Konkuk University, Seoul 143-701, Korea .

Abstract

Abnormal neuronal aggregation of alpha-synuclein is implicated in the development of many neurological disorders, including Parkinson disease and dementia with Lewy bodies. Glial cells also show extensive alpha-synuclein pathology and may contribute to disease progression. However, the mechanism that produces the glial alpha-synuclein pathology and the interaction between neurons and glia in the disease-inflicted microenvironment remain unknown. Here, we show that alpha-synuclein proteins released from neuronal cells are taken up by astrocytes through endocytosis and form inclusion bodies. The glial accumulation of alpha-synuclein through the transmission of the neuronal protein was also demonstrated in a transgenic mouse model expressing human alpha-synuclein. Furthermore, astrocytes that were exposed to neuronal alpha-synuclein underwent changes in the gene expression profile reflecting an inflammatory response. Induction of pro-inflammatory cytokines and chemokines correlated with the extent of glial accumulation of alpha-synuclein. Together, these results suggest that astroglial alpha-synuclein pathology is produced by direct transmission of neuronal alpha-synuclein aggregates, causing inflammatory responses. This transmission step is thus an important mediator of pathogenic glial responses and could qualify as a new therapeutic target.

PMID:
20071342
PMCID:
PMC2838344
DOI:
10.1074/jbc.M109.081125
[Indexed for MEDLINE]
Free PMC Article
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