Recent advances on the pathogenesis of Huntington's disease |
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| Authors: | Petersén A Mani K Brundin P |
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| Affiliation: | 1. Atherothrombosis Research Center/Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, Ioannina, Greece;2. Department of Cardiology, School of Medicine, University of Ioannina, Ioannina, Greece;1. Brain and Mind Centre, Sydney Medical School, University of Sydney, Australia;2. Western Clinical School, University of Sydney, Australia;3. School of Medical Sciences, University of New South Wales, Australia;4. National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Australia |
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| Abstract: | We review recent advances regarding the pathogenesis of Huntington's disease (HD). This genetic neurodegenerative disorder is caused by an expanded CAG repeat in a gene coding for a protein, with unknown function, called huntingtin. There is selective death of striatal and cortical neurons. Both in patients and a transgenic mouse model of the disease, neuronal intranuclear inclusions, immunoreactive for huntingtin and ubiquitin, develop. Huntingtin interacts with the proteins GAPDH, HAP-1, HIP1, HIP2, and calmodulin, and a mutant huntingtin is specifically cleaved by the proapoptotic enzyme caspase 3. The pathogenetic mechanism is not known, but it is presumed that there is a toxic gain of function of the mutant huntingtin. Circumstantial evidence suggests that excitotoxicity, oxidative stress, impaired energy metabolism, and apoptosis play a role. |
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