Frederic Saudou, PhD, Université Grenoble Alpes, Grenoble, France, explains the role of huntingtin (HTT) in neuronal transport and how this is affected by mutations in the protein as part of Huntington’s disease (HD). HTT is a membrane-associated scaffolding protein that associates with the molecular motor complex, anchoring vesicles to microtubules and facilitating the transport of many key neuronal proteins, including BDNF. When HTT is mutated as in HD, these vesicles detach from microtubules and transport efficiency is reduced. Diminished BDNF transport leads to reduced BDNF delivery to the striatum, which is not produced in the striatal neurons themselves. The resultant weakened downstream pro-survival signaling contributes to striatal and cortical neuronal death. Recent studies have shown that the movement of neurotrophic factors and neurotransmitters is altered not only in HD, but also in other neurological diseases. This interview took place during the European Huntington’s Disease Network 2022 Plenary Meeting.
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