title: Cognitive dysfunction in Huntington's disease: mechanisms and therapeutic strategies beyond BDNF.
abstract: One of the main focuses in Huntington's disease (HD) research, as well as in most neurodegenerative diseases, is the development of new therapeutic strategies, as currently there is no treatment to delay or prevent the progression of the disease. Neuronal dysfunction and neuronal death in HD are caused by a combination of interrelated pathogenic processes that lead to motor, cognitive and psychiatric symptoms. Understanding how mutant huntingtin impacts on a plethora of cellular functions could help to identify new molecular targets. Although HD has been classically classified as a neurodegenerative disease affecting voluntary movement, lately cognitive dysfunction is receiving increased attention as it is very invalidating for patients. Thus, an ambitious goal in HD research is to find altered molecular mechanisms that contribute to cognitive decline. In this review, we have focused on those findings related to corticostriatal and hippocampal cognitive dysfunction in HD, as well as on the underlying molecular mechanisms, which constitute potential therapeutic targets. These include alterations in synaptic plasticity, transcriptional machinery and neurotrophic and neurotransmitter signaling.
authors.affiliation: Departament de Biomedicina, Facultat de Medicina, Universitat de Barcelona, Barcelona, Catalonia, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.|Centro de Investigación Biomédica en Red (CIBER) sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Puigdellívol
authors.affiliation: Departament de Biomedicina, Facultat de Medicina, Universitat de Barcelona, Barcelona, Catalonia, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.|Centro de Investigación Biomédica en Red (CIBER) sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.|Institut de Neurociències, Universitat de Barcelona, Catalonia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Saavedra
authors.affiliation: Departament de Biomedicina, Facultat de Medicina, Universitat de Barcelona, Barcelona, Catalonia, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.|Centro de Investigación Biomédica en Red (CIBER) sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.|Institut de Neurociències, Universitat de Barcelona, Catalonia, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Pérez-Navarro
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000627:therapeutic use; D003072:Cognition Disorders / Q000209:etiology* / Q000628:therapy*; D004195:Disease Models, Animal; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000150:complications*; D009434:Neural Pathways / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020662:Guanine Nucleotide Exchange Factors; C503866:KALRN protein, human; D017346:Protein Serine-Threonine Kinases
keywords: A2AR; GluN3A; Kalirin-7; PDEs; PKA; cGMP; nSOC; p75NTR