SIG | Basic Mechanisms and Neuroscience of Epilepsy: mTOR Dysregulation in Epilepsy – Targets and Pathways Beyond the Usual Suspects
Friday, December 3, 2021
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OVERVIEW:
This Special Interest Group discusses novel mechanistic target of rapamycin (mTOR) signaling components, their dysregulation, and how and if they could serve as potential treatment targets.
The mTOR pathway is highly conserved across species and is ubiquitously found in numerous cell types, where one of its basic functions is the regulation of protein synthesis. Abnormal mTOR activation can negatively impact these systems, resulting in the instability of neural circuitries by promoting neuronal hyperexcitability. Consequently, mTOR hyperactivation is associated with the construction and maintenance of epileptic networks, as well as with cognitive defects in drug-resistant human epilepsies and in experimental models. Previous work has focused mostly on determining the roles of dysregulated mTOR or MTORC1, but more recently, other upstreamand downstream components of this pathway have come into focus as important mediators of mTORopathy-associated epilepsies
Learning Objectives:
Following participation in this activity, participants will be able to:
- Understand novel signaling molecules that are upstream and downstream of the mTOR cascade, which aberrant activation or deactivation result in neuronal hyperexcitability
- Learn how mTOR signaling contributes to seizures, and to learn of novel findings implicating theSzt2 gene in the pathophysiology of epilepsy
- Understand how mTORC1-mediated cap-dependent translation regulates 4EBP1/2 and promotes epilepsy
Program:
SIG Coordinators: Amy L. Brewster, PhD and Matthew Weston, PhD
Chair: Amy L. Brewster, PhD
Presenting Data Supporting that Altered 4EBP1/2-Regulated Translation Contributes to Focal Cortical Malformations, Neuronal Morphological and Functional Defects, and Seizures in an In Utero Electroporation-Based Mouse Model of mTORopathy | Lena Nguyen, PhD
Presenting Mouse Model Data of Szt2 Loss-of-Function Resulting in Neurodevelopmental Disease and Epilepsy | Matthew Weston, PhD
Presenting depdc5/mTOR-Related Epilepsy | Christopher Yuskaitis, MD, PhD