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UID:20251107T161338EST-7320GMLkTz@132.216.98.100
DTSTAMP:20251107T211338Z
DESCRIPTION:\nSupported by the generosity of the Killam Trusts\, The Neuro'
 s Killam Seminar Series invites outstanding guest speakers whose research 
 is of interest to the scientific community at The Neuro and 51³Ô¹ÏÍøUnivers
 ity.\n\n\nRegister Now\n\nTo watch online\, click here\n\nHost: Gary Armst
 rong\n\n\n\n	When Protection Fails: How Loss of TDP-43 SUMOylation Primes t
 he Nervous System for Degeneration\n\n\nMaxime W. Rousseaux\, Ph.D.\n\n\n	A
 ssociate professor and Canada Research Chair Tier II\n		Co-Director\, GEM Co
 re\n		Department of Cellular and Molecular Medicine\n		University of Ottawa Br
 ain and Mind Research Institute\n\n\n \n\nAbstract: TDP-43 mislocalization
  and aggregation are defining features of amyotrophic lateral sclerosis (A
 LS) and frontotemporal dementia (FTD). Building on our previous work ident
 ifying stress-dependent SUMOylation of TDP-43 at lysine 408 (K408)\, we ex
 amined whether loss of this modification drives neurodegeneration and how 
 additional genetic or environmental stressors shape disease-relevant outco
 mes. Using Tdp-43^K408R knock-in mice\, which lack this SUMOylation site\,
  we assessed age-related pathology through behavioural\, histological\, an
 d neuromuscular junction analyses\, and further challenged animals with AL
 S/FTD-linked insults including a C9ORF72 repeat expansion and traumatic br
 ain injury. Complementary studies employed human iPSC-derived motor neuron
 s engineered with the K408R mutation. Aging Tdp-43^K408R mice developed sp
 inal cord TDP-43 mislocalization\, neuromuscular denervation\, and mild co
 gnitive impairment by 18 months\, though phenotypes were modest—likely ref
 lecting limited stress exposure under standard housing conditions. Nonethe
 less\, combining TDP-43 SUMOylation deficiency with C9ORF72 expansion or t
 raumatic injury exacerbated select behavioural and histopathological abnor
 malities. In parallel\, the K408R mutation in human motor neurons altered 
 TDP-43 SUMOylation and is being used to probe human-specific mechanisms. T
 ogether\, these findings indicate that stress-dependent SUMOylation of TDP
 -43 is neuroprotective and that loss of this modification heightens vulner
 ability to genetic and environmental challenges\, underscoring posttransla
 tional regulation of TDP-43 as a potential therapeutic avenue in ALS and F
 TD.\n\nBio: Dr. Rousseaux is an Associate Professor and Canada Research Ch
 air at uOttawa where his lab looks at how protein mislocalization drives n
 eurodegeneration. His research group leverages high throughput screens and
  mouse genetics to examine the interplay between genes and environment in 
 the context of disease. Dr. Rousseaux is recipient of funding from federal
  (CIHR\, NSERC) and non-profit (ALS Canada\, ASAP) funding sources and is 
 a Fahn Scholar of the Parkinson’s Foundation and Brain Canada Future Leade
 r.\n
DTSTART:20251111T210000Z
DTEND:20251111T220000Z
LOCATION:de Grandpre Communications Centre\, The Neuro
SUMMARY:Killam Seminar Series: When Protection Fails: How Loss of TDP-43 SU
 MOylation Primes the Nervous System for Degeneration
URL:/neuro/channels/event/killam-seminar-series-when-p
 rotection-fails-how-loss-tdp-43-sumoylation-primes-nervous-system-368743
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