Gene-environment interactions, neuronal dysfunction and pathological plasticity in Huntington's disease

Anton Van Dellen, Helen E. Grote, Anthony J. Hannan*

*Corresponding author for this work

Research output: Contribution to journalShort surveypeer-review

51 Citations (Scopus)

Abstract

1. Huntington's disease (HD) is a fatal autosomal dominant disorder in which there is progressive neurodegeneration producing motor, cognitive and psychiatric symptoms. The dynamic mutation that causes the disease is common to numerous other brain disorders, which may share similar pathogenic mechanisms. 2. Much progress has been made in the past decade in understanding how a trinucleotide (CAG) repeat expansion, encoding an expanded polyglutamine tract in the huntingtin protein, induces dysfunction at molecular and cellular levels. The present review integrates various lines of experimental evidence in an attempt to move towards a unifying mechanistic framework, which may explain the pathogenesis of HD, from molecular through to neuronal network and behavioural levels. 3. Recent evidence, using transgenic mouse models, also suggests that environmental factors can modify the onset and progression of HD. The effects of specific environmental manipulations are discussed in the context of gene-environment interactions and experience-dependent plasticity in the healthy and diseased brain, particularly the cerebral cortex.

Original languageEnglish
Pages (from-to)1007-1019
Number of pages13
JournalClinical and Experimental Pharmacology and Physiology
Volume32
Issue number12
DOIs
Publication statusPublished - Dec 2005
Externally publishedYes

Keywords

  • Cerebral cortex
  • Cognitive disorder
  • Environmental enrichment
  • Gene-environment interaction
  • Huntington's disease
  • Neurodegeneration
  • Polyglutamine
  • Synaptic dysfunction
  • Synaptic plasticity
  • Trinucleotide repeat expansion

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