Modeling mTORopathies in zebrafish

The intracellular mTOR pathway plays a pivotal role in major cellular functions in the human body. Genetic mutations in genes that encode for proteins that normally keep the activity of mTOR under control, leads to overactivation of the pathway. This plays a key role in the pathogenesis of some neurological disorders grouped under the term 'mTORopathies'. We aim to model these pathologies in genetically modified zebrafish, as they offer the possibility to study the involvement of specific proteins in the origin of human disease to prove causality. For that purpose, we will investigate the seizure behavior in mutant zebrafish larvae, and monitor their brain activity and cognitive disability. We will also examine their structural brain malformations, and aim to get a thorough insight into changes in the global protein expression of the brain structures. Finally, we want to explore the pharmacological potential of a common mTOR inhibitor, rapamycin, as possible medication for the treatment and prevention of mTORopathies in general. This in vivo functional study in zebrafish will help us to understand better the pathophysiology of mTORopathies, and additionally will form a starting point for pharmacological studies, which may uncover potential therapeutic strategies for improved seizure control.

Jaar van publicatie:2022

Toegankelijkheid:Open