Insights into GABA A ergic system alteration in Huntington's disease

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Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disease that is characterized by a triad of motor, psychiatric and cognitive impairments. There is still no effective therapy to delay or halt the disease progress. The striatum and cortex are two particularly affected brain regions that exhibit dense reciprocal excitatory glutamate and inhibitory gamma-amino butyric acid (GABA) connections. Imbalance between excitatory and inhibitory signalling is known to greatly affect motor and cognitive processes. Emerging evidence supports the hypothesis that disrupted GABAergic circuits underlie HD pathogenesis. In the present review, we focused on the multiple defects recently found in the GABAergic inhibitory system, including altered GABA level and synthesis, abnormal subunit composition and distribution of GABAA receptors and aberrant GABAA receptor-mediated signalling. In particular, the important role of cation-chloride cotransporters (i.e. NKCC1 and KCC2) is discussed. Recent studies also suggest that neuroinflammation contributes significantly to the abnormal GABAergic inhibition in HD. Thus, GABAA receptors and cation-chloride cotransporters are potential therapeutic targets for HD. Given the limited availability of therapeutic treatments for HD, a better understanding of GABAergic dysfunction in HD could provide novel therapeutic opportunities.




Hsu, Y. T., Chang, Y. G., & Chern, Y. (2018, December 1). Insights into GABA A ergic system alteration in Huntington’s disease. Open Biology. Royal Society Publishing.

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