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SUMMARY:BMI Thesis Prize 2022 SEMINAR // Nathan Riguet "Disentangling the 
 mechanisms of inclusions formation in Huntington's disease (HD): The need 
 for more disease-relevant models"
DTSTART:20221221T121500
DTEND:20221221T130000
DTSTAMP:20260506T111933Z
UID:4bc4f8897ad10af4b500e98642555c43bf9ce46a2998b45ec9047560
CATEGORIES:Conferences - Seminars
DESCRIPTION:Nathan Riguet\,  LMNN – Lashuel Lab\, BMI\nDespite the fact
  that the gene responsible for Huntington’s disease (HD) is known\, we s
 till do not understand the underlying mechanisms leading to neurodegenerat
 ion and death. Identifying and understanding the mechanisms controlling mu
 tant huntingtin (mHtt) aggregation and inclusion formation using different
  cellular and animal models is crucial to elucidate the molecular mechanis
 ms underpinning the disease and to develop effective treatments to prevent
  or slow the progression of HD.\nAt the mechanistic level\, our work shows
  that mHtt aggregation and inclusion formation in the cytosol and nucleus 
 occur via different mechanisms and lead to the formation of inclusions wit
 h distinct biochemical and ultrastructural properties. We show that mHtt c
 ytoplasmic inclusion formation occurs first with the rapid formation of a
  dense fibrillar core driven predominantly by intermolecular interactions 
 involving the polyQ domain via phase separation-like mechanisms. A second 
 phase is associated with the recruitment of soluble mHtt\, fibril growth\,
  and the active recruitment and sequestration of lipids\, proteins\, and m
 embranous organelles. Using primary neurons\, we demonstrated that neurona
 l intranuclear inclusions evolve from small aggregates to large granulo-fi
 lamentous inclusions associated with cellular toxicity over time. \nFinal
 ly\, we would like to emphasize that our comparative analysis of tag-free 
 and GFP-tagged mutant mHtt aggregation and inclusions formation will infor
 m future efforts to develop models that reproduce HD pathology more faithf
 ully and underscore the need for developing label-free techniques to inves
 tigate disease-relevant mechanisms that underpin inclusion formation.\n 
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717 https://epfl.zoom.u
 s/j/62550191552?pwd=OFRDVzBHb0cyVG1wYkxUSFFEMUNPdz09
STATUS:CONFIRMED
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