Molecular mediators, environmental modulators and experience-dependent synaptic dysfunction in Huntington's disease

• Autorzy: Hannan A. J.
• Języki publikacji: EN

Abstrakty

EN

Huntington's disease (HD) is an autosomal dominant disorder in which there is pro­gressive neurodegeneration producing motor, cognitive and psychiatric symptoms. HD is caused by a trinucleotide (CAG) repeat mutation, encoding an expanded polyglutamine tract in the huntingtin protein. At least eight other neurodegenerative diseases are caused by CAG/glutamine repeat expansions in different genes. Recent evidence suggests that environmental factors can modify the onset and progression of Huntington's disease and possibly other neurodegenerative disorders. This re­view outlines possible molecular and cellular mechanisms mediating the polyglutamine-induced toxic 'gain of function' and associated gene-environment interactions in HD. Key aspects of pathogenesis shared with other neurodegenerative diseases may include abnormal protein-protein interactions, selective disruption of gene expression and 'pathological plasticity' of synapses in specific brain regions. Recent discoveries regarding molecular mechanisms of pathogenesis are guiding the development of new therapeutic approaches. Knowledge of gene-environment interactions, for example, could lead to development of ‘enviromimetics’ which mimic the beneficial effects of specific environmental stimuli. The effects of environmental enrichment on brain and behaviour will also be discussed, together with the general implications for neuroscience research involving animal models.

Słowa kluczowe

EN

synaptic plasticity; environmental enrichment; polyglutamine; trinucleotide repeat; Huntington's disease; gene-environment interaction

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2004
• Tom: 51
• Numer: 2
• Opis fizyczny: p.415-430,fig.,ref.

Twórcy

autor

Hannan A. J.

• University of Melbourne, Victoria 3010, Australia

Bibliografia

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