The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity
Open accessAbstract
Huntington disease (HD) is characterized by the preferential loss of striatal medium-sized spiny neurons (MSNs) in the brain. Because MSNs receive abundant glutamatergic input, their vulnerability to excitotoxicity may be largely influenced by the capacity of glial cells to remove extracellular glutamate. However, little is known about the role of glia in HD neuropathology. Here, we report that mutant huntingtin accumulates in glial nuclei in HD brains and decreases the expression of glutamate transporters. As a result, mutant huntingtin (htt) reduces glutamate uptake in cultured astrocytes and HD mouse brains. In a neuron–glia coculture system, wild-type glial cells protected neurons against mutant htt-mediated neurotoxicity, whereas glial cells expressing mutant htt increased neuronal vulnerability. Mutant htt in cultured astrocytes decreased their protection of neurons against glutamate excitotoxicity. These findings suggest that decreased glutamate uptake caused by glial mutant htt may critically contribute to neuronal excitotoxicity in HD.
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Cited by
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Metadata
- Authors
- Shin, J.-Y., Fang, Z.-H., Yu, Z.-X., Wang, C.-E., Li, S.-H., & Li, X.-J.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2005-12-19
- Volume
- 171
- Issue
- 6
- Pages
- 1001-1012
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2052935486
- Cited by
- 477
- References
- 49
- FWCI
- 6.23
- Type
- journal article
- Language
- en
- Open access
- green
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- Shin, J.-Y., Fang, Z.-H., Yu, Z.-X., Wang, C.-E., Li, S.-H., & Li, X.-J. (2005). Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200508072
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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