Exploring extracellular small RNAs as potential early biomarkers and mediators in the pathogenesis of Huntington’s disease

[eng] Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder caused by an expansion of CAG triplets in the huntingtin gene (HTT). The main neuropathological signs of HD include the presence of cytoplasmic aggregates of the protein produced by mutated HTT (mHTT), massive...

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Detalles Bibliográficos
Autor: Herrero Lorenzo, Marina
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/217435
Acceso en línea:https://hdl.handle.net/2445/217435
http://hdl.handle.net/10803/693327
Access Level:acceso abierto
Palabra clave:Marcadors bioquímics
Citogenètica
Corea de Huntington
Micro RNAs
Biochemical markers
Cytogenetics
Huntington's chorea
MicroRNAs
Descripción
Sumario:[eng] Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder caused by an expansion of CAG triplets in the huntingtin gene (HTT). The main neuropathological signs of HD include the presence of cytoplasmic aggregates of the protein produced by mutated HTT (mHTT), massive loss of medium spiny neurons in the striatum, and cortical degeneration. In current clinical practice, symptomatic patients are diagnosed based on the appearance of a complex constellation of clinical symptoms, including progressive motor abnormalities, neuropsychiatric disorders, early cognitive impairment, and dementia, among others. However, genetic analysis allows the use of predictive tests to identify carriers of the genetic mutation in presymptomatic phases, who may present progressive brain changes and alterations in cognitive performance long before the diagnosis of the disease characterized by the appearance of motor symptoms. Current treatments for HD only provide symptomatic relief, and the most recent results from clinical trials investigating gene therapies have not shown significant efficacy so far. Combining predictive genetic testing with novel molecular biomarkers at early stages could help improve clinical trial design for HD, by selecting the most appropriate patients, stratification of patients for interventions, monitoring response to treatment, and improving the efficiency of new clinical trials.