title: The Biology of Huntingtin.
abstract: Huntingtin (HTT) is now a famous protein because an abnormal expansion of a glutamine stretch (polyQ) in its N-terminal sequence leads to the devastating neurodegenerative disorder Huntington's disease (HD). The gene encoding huntingtin, HTT, and its dominantly inherited mutation were identified more than 20 years ago. Subsequently, in the hope of finding a cure for HD, there has been intense research aimed at understanding the molecular mechanisms underlying the deleterious effects of the presence of the abnormal polyQ expansion in HTT. Notwithstanding with the value of this approach, evidence has been emerging of a potential role of context and function of the HTT protein in the specificity and severity of the pathogenicity. HTT is ubiquitous both at the tissue and subcellular levels. It interacts with many partners and has long been considered having no clearly defined cellular function. Based on research over the past 20 years, specifically focused on the function of wild-type HTT, we reconsider the literature describing HTT-regulated molecular and cellular mechanisms that could be dysfunctional in HD and their possible physiological consequences for patients.
authors.affiliation: University Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, 38000 Grenoble, France; INSERM, U1216, 38000 Grenoble, France; CHU Grenoble Alpes, 38000 Grenoble, France. Electronic address: frederic.saudou@inserm.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Saudou
authors.affiliation: University Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, 38000 Grenoble, France; INSERM, U1216, 38000 Grenoble, France. Electronic address: sandrine.humbert@univ-grenoble-alpes.fr.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Humbert
mesh_terms: D000818:Animals; D001695:Biology; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000150:complications / Q000235:genetics / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins