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Corticostriatal circuit dysfunction in Huntington's disease: intersection of glutamate, dopamine and calcium.

ABSTRACT: Huntington's disease (HD) is a noncurable and progressive autosomal-dominant neurodegenerative disorder that results from a polyglutamine expansion in the amino-terminal region of the huntingtin protein. The generation of rodent HD models has revealed that cellular dysfunction, rather than cell death alone, occurs early in the disease progression, appearing even before overt symptom onset. Much evidence has now established that dysfunction of the corticostriatal circuit is key to HD symptomology. In this article, we summarize the most current findings that implicate glutamate, dopamine and calcium signaling in this system and discuss how they work in concert to disrupt corticostriatal function. In addition, we highlight therapeutic strategies related to altered corticostriatal signaling in HD.

SUBMITTER: Miller BR

PROVIDER: S-EPMC3184508 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Corticostriatal circuit dysfunction in Huntington's disease: intersection of glutamate, dopamine and calcium.

Miller Benjamin Ray BR Bezprozvanny Ilya I

Future neurology 20100901 5

Huntington's disease (HD) is a noncurable and progressive autosomal-dominant neurodegenerative disorder that results from a polyglutamine expansion in the amino-terminal region of the huntingtin protein. The generation of rodent HD models has revealed that cellular dysfunction, rather than cell death alone, occurs early in the disease progression, appearing even before overt symptom onset. Much evidence has now established that dysfunction of the corticostriatal circuit is key to HD symptomology ...[more]

PMID: 21977007

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