Gene-Environment Interactions in Neurodegenerative Diseases

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Neurodegenerative disorders affect a large proportion of human populations and many are increasing in their prevalence due to extended life spans and elevated risk of neurodegeneration with age. Recent decades have seen great progress in understanding genetic contributions to neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and motor neuron disease. Transgenic animal models of neurodegenerative disease have allowed gene–environment interactions to be explored, first in HD and then in AD and other neurodegenerative disorders. Research involving transgenic mouse models of HD has shown that environment enrichment dramatically delays the onset and progression of the disease. These gene–environment interactions in animal models of neurodegenerative disease, together with epidemiological studies, suggest that therapy based on elevated levels of mental and physical activity might benefit those at risk of, or suffering from, these diseases. Furthermore, environmental manipulations of animal models provide insight into possible mechanisms of neurodegeneration and subsequent identification of novel therapeutic targets (enviromimetics). The epidemiology of neurodegenerative diseases, which is most extensive for AD and other forms of dementia, implicates not only levels of mental and physical activity but also diet and, in some cases, other environmental factors such as neurotoxin exposure and brain trauma.

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