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PRODID:-//Memento EPFL//
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SUMMARY:BMI Progress Reports 2021 // Prof. Lashuel's Lab\, N. Riguet "Mech
 anisms of inclusion formation in Huntington’s disease: Lessons from cell
 ular models"
DTSTART:20210210T121500
DTEND:20210210T130000
DTSTAMP:20260408T005715Z
UID:2a481133829b31a05ef1323b82a517c1889f4e246d952449f4e1fe17
CATEGORIES:Conferences - Seminars
DESCRIPTION:N. Riguet\nHuntington’s Disease (HD) is a genetic\, progress
 ive neurodegenerative disorder characterized by motor\, cognitive and psyc
 hiatric symptoms. Despite the strong evidence linking the aggregation of t
 he Huntingtin protein (Htt) to the pathogenesis of Huntington’s disease 
 (HD)\, the mechanisms underlying Htt aggregation and neurodegeneration are
  not yet fully understood. This knowledge is crucial for developing reliab
 le preclinical models and to develop effective therapies and disease modif
 ying strategies.\nTowards addressing this knowledge gap\, we investigated 
 the mechanisms of Htt aggregation and inclusion formation in cellular mode
 ls of HD. We applied correlative light- and electron microscopy (CLEM) and
  quantitative proteomics to investigate the ultrastructural properties and
  protein composition of cytoplasmic and nuclear Htt aggregates (inclusions
 ) formed in both mammalian cells and neurons. Our findings provide novel i
 nsight into the ultrastructural properties of cytoplasmic and nuclear Htte
 x1 inclusions and their mechanisms of formation. We show that Httex1 inclu
 sion formation and maturation are complex multi-stage processes that are d
 riven and modulated by specific sequences of the exon1 and involve the seq
 uestration of lipids\, cytoplasmic and cytoskeletal proteins related to HD
  dysregulated pathways. We also show that formation of Httex1 inclusions f
 ormation lead to the accumulation of remodeled or dysfunctional membranous
  organelles and the impairment of the protein quality control and degradat
 ion machineries. Interestingly\, nuclear and cytoplasmic Httex1 inclusions
  exhibited distinct biochemical composition and ultrastructural properties
 \, suggesting that the cellular environment is an important determinant of
  Htt aggregation and toxicity. These findings and their implication for th
 e understanding of the pathogenesis of HD and developing novel therapeutic
  approaches for treating HD will be discussed.\n 
LOCATION:Online
STATUS:CONFIRMED
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