BEGIN:VCALENDAR VERSION:2.0 PRODID:-//132.216.98.100//NONSGML kigkonsult.se iCalcreator 2.20.4// BEGIN:VEVENT UID:20250930T023110EDT-1249dTZs9G@132.216.98.100 DTSTAMP:20250930T063110Z DESCRIPTION:The Killam Seminar Series presents 'Therapeutic strategies for treating synaptic dysfunction in amyotrophic lateral sclerosis (ALS) and f rontotemporal dementia (FTD)”\n\nRegistration available here. \n\nSpeaker: Chantelle Sephton\, PhD\n Associate Professor\, Université Laval\, Canada \n\nAbstract: Synaptic dysfunction is common among all neurodegenerative d iseases. Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia ( FTD) are two related neurodegenerative diseases where dendritic attrition and synaptic loss occurs prior to clinical and pathological symptoms of th e disease. Through poorly defined mechanisms\, changes to the structure an d function of affected neuron populations in patients with ALS and FTD are initiated by mislocalized or aggregated proteins\, which triggers a vicio us cycle between microglia activation\, neuroinflammation\, and proteotoxi city. We present work demonstrating that neuron-specific expression of a d isease-linked ALS mutation\, fused in sarcoma (FUS) R521G\, in mice is suf ficient to trigger dendritic attrition and loss of synapses. We find that changes to neuronal integrity precede the activation of astrocytes and mic roglia. Based on these observations\, we are investigating two therapeutic strategies\, 1) reducing inflammation through drug-targeted inhibition of the NF-kB pathway and 2) restoring proteostasis through drug-targeted upr egulation of heat-shock proteins using histone deacetylases (HDAC) inhibit ors and HSP inducers\, both of which are aimed at maintaining the neuronal integrity in patients with ALS or FTD. Our findings reveal that both ther apeutic approaches restore cognitive and motor function as well as increas e dendritic branching and spine numbers in ALS-FUSR521G mouse models. Addi tionally\, both approaches restore altered FUS proteostasis and reduce the activation of astrocytes and microglia. Future work will assess the speci fic effects of these drugs on cell-types and their ability to restore neur onal function. Together\, these discoveries have elucidated the contributi on of FUS to synaptic health and dysfunction and identified strategies to treating synaptic dysfunction associated with ALS and FTD.\n\nBio: Dr. Cha ntelle F. Sephton received her Bachelor’s of Science in Biochemistry from the University of Saskatchewan in Saskatoon (2002) and her PhD in Psychiat ry from the University of Saskatchewan (2007). She did her postdoctoral st udies at the University of Texas (UT) Southwestern Medical Center at Dalla s under the mentorship of Dr. Gang Yu in the Department of Neuroscience (2 007-2014). She started her lab at Université Laval in the CERVO Brain Rese arch Centre in 2014 and is currently an Associate Professor in the departm ent of psychiatry and neuroscience.\n\nDr. Sephton’s research interests ar e focused on understanding how translation at the synapse is regulated and how disruption of local translation leads to neurodegeneration. In partic ular\, her research program is identifying the mechanisms by which disease -linked RNA-binding proteins cause synaptic loss and promote amyotrophic l ateral sclerosis (ALS) and frontotemporal dementia (FTD)\, neurodegenerati ve diseases that affect over 40\,000 people in Canada. This work stems fro m the discovery that RNA-binding proteins including TDP-43 and FUS are mut ated in familial forms of ALS and FTD. Mutations in these proteins result in their cytoplasmic mislocalization and aggregation\, which are thought t o contribute to neurodegeneration in these diseases. Stemming from her pos t-doctoral work and the discovery of the biological functions of disease-l inked RNA-binding proteins\, her current work now focuses on: 1) understan ding the mechanisms by which disease-associated mutations of TDP-43 and FU S influence RNA metabolism and synaptic function\; 2) investigating the ef fects of disease-linked RNA-binding proteins on non-cell-autonomous contri butions to developing disease phenotypes\; and 3) Identifying and testing therapeutic approaches to treating ALS and FTD.\n\n\nSupported by the gene rosity of the Killam Trusts \, The Neuro’s Killam Seminar series hosts out standing guest speakers whose research is of interest to the scientific co mmunity at The Neuro and 9I.\n DTSTART:20220222T210000Z DTEND:20220222T220000Z SUMMARY:Killam Seminar Series presents 'Therapeutic strategies for treating synaptic dysfunction in amyotrophic lateral sclerosis (ALS) and frontotem poral dementia (FTD)”' URL:/neuro/channels/event/killam-seminar-series-presen ts-therapeutic-strategies-treating-synaptic-dysfunction-amyotrophic-337781 END:VEVENT END:VCALENDAR