Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Tots els drets reservats
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/183269
Cognitive dysfunction in Huntington¿s disease: Humans, mouse models and molecular mechanisms
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder due to an expanded CAG/polyglutamine repeat in the coding region of the huntingtin (htt) gene that causes the preferential degeneration of striatal neurons. Although HD is classically considered a motor disorder, cognitive decline manifests even before the appearance of motor symptoms, and reflects the impairment of additional neuronal populations, such as cortical and hippocampal neurons, in the presence of mutant htt (mhtt). Studies on cognitive dysfunction in HD patients have focused on the cortico-striatal pathway. Here we will describe that HD patients and mouse models share many cognitive defects. Alterations in hippocampal synaptic plasticity and function found in HD mouse models highlight that changes in the functioning of the hippocampal formation contribute to cognitive dysfunction in humans. The similarity between the cognitive dysfunction in HD patients and mouse models has helped to understand better how cognitive dysfunction takes place. Moreover, it validates the use of HD mice to study the molecular mechanisms involved in HD cognitive decline. Several studies in HD mouse models indicate that altered synaptic composition/function, deficient neurotrophic support, kinase/phosphatase imbalance, and transcription dysregulation play an important role in cognitive impairment. This knowledge opens the possibility of identifying relevant therapeutic targets to fight cognitive decline in HD. The finding that in HD many mechanisms are similarly altered in hippocampal and striatal neurons suggests the possibility of a common therapeutic strategy to ameliorate both cognitive and motor dysfunction.
Matèries (anglès)
Citació
Citació
GIRALT TORROELLA, Albert, SAAVEDRA, Ana, ALBERCH I VIÉ, Jordi, PÉREZ NAVARRO, Esther. Cognitive dysfunction in Huntington¿s disease: Humans, mouse models and molecular mechanisms. _Journal of Huntington's disease_. 2012. Vol. 1, núm. 155-173. [consulta: 24 de gener de 2026]. ISSN: 1879-6397. [Disponible a: https://hdl.handle.net/2445/183269]