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Targeting Glial Cells to Elucidate the Pathogenesis of Huntington’s Disease

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Abstract

Huntington’s disease (HD) is a hereditary neurodegenerative disorder caused by expended CAG repeats in the Huntingtin (Htt) gene. The resultant mutant Htt (mHtt) forms aggregates in neurons and causes neuronal dysfunctions. The major characteristic of HD is the selective loss of neurons in the striatum and cortex, which leads to movement disorders, dementia, and eventual death. Expression of mHtt was also found in non-neuronal cells in the brain, suggesting non-cell-autonomous neurotoxicity in HD. As was documented in many different neurodegenerative disorders, elevated inflammatory responses are also reported in HD. To date, effective treatments for this devastating disease remain to be developed. This review focuses on the importance of glial cells and inflammation in HD pathogenesis. Potential anti-inflammatory interventions for HD are also discussed.

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Abbreviations

Aβ:

Amyloid β peptide

AD:

Alzheimer’s disease

ALS:

Amyotrophic lateral sclerosis

BDNF:

Brain-derived neurotrophic factor

CNS:

Central nervous system

GLT1:

Astroglial glutamate transporter

Htt:

Huntingtin

HD:

Huntington’s disease

mHtt:

Mutant Htt

iNOS:

Inducible nitric oxide synthase

NO:

Nitric oxide

polyQ:

Polyglutamine

ROS:

Reactive oxygen species

WT:

Wildtype

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Acknowledgments

We thank Mr. Dan Chamberlin and Ms. Ihua Hsieh for reading and editing the manuscript, and Mr. Jung-Rung Hung for the artwork. This work was supported by grants (NSC97-2321-B-001-030) from the National Science Council and Academia Sinica, Taipei, Taiwan.

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Authors and Affiliations

  1. Division of Neuroscience, Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan

    Han-Yun Hsiao & Yijuang Chern

  2. Institute of Neuroscience, National Yang Ming University, Taipei, 11529, Taiwan

    Han-Yun Hsiao & Yijuang Chern

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  1. Han-Yun Hsiao
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  2. Yijuang Chern
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Correspondence to Yijuang Chern.

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Hsiao, HY., Chern, Y. Targeting Glial Cells to Elucidate the Pathogenesis of Huntington’s Disease. Mol Neurobiol 41, 248–255 (2010). https://doi.org/10.1007/s12035-009-8097-5

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  • DOI: https://doi.org/10.1007/s12035-009-8097-5

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