title: Recent advances on the pathogenesis of Huntington's disease.
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.
authors.affiliation: Department of Physiological Sciences, Wallenberg Neuroscience Center, Sölvegatan 17, Lund, 222 52, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Petersén
authors.forename: K
authors.initials: K
authors.lastname: Mani
authors.forename: P
authors.initials: P
authors.lastname: Brundin
mesh_terms: D000818:Animals; D006801:Humans; D006816:Huntington Disease / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008959:Models, Neurological; D009462:Neurology / Q000639:trends*