Is Huntington disease –a late onset neurological condition- a neurodevelopmental disorder?
DR INSERM, team leader: Équipe « Progéniteurs neuraux et pathologies cérébrales » Grenoble Institut des Neurosciences – INSERM U836 – UGA
Huntington Disease (HD) belongs to the family of late onset manifesting neurological disorders including Alzheimer and Parkinson diseases. The cause of HD is the presence of an abnormal expansion of a polyglutamine tract in the huntingtin (HTT) protein. HD is characterized by a long premanifest phase before onset of progressive neurological and psychiatric symptoms at adult age, yet mutant HTT (mHTT) is expressed from the very beginning of life. Anyway, given the adult onset and dysfunction and death of adult neurons characterizing HD, most studies have focused on the toxic effects elicited by mutant HTT in post-mitotic neurons and the roles of the wild-type protein during development have been overlooked. We will discuss how HTT regulates several steps of mouse embryonic corticogenesis. HTT is crucial to maintain the pool of cycling progenitors and for the migration and post-natal maturation of post-mitotic neurons. We will describe the underlying molecular mechanisms by which HTT mediates its effects. Finally, we will also show the consequences of the presence of an abnormal polyglutamine expansion in HTT during cortical neurogenesis and consider the viewing of HD as a developmental disorder.
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