Description:

"Deregulated autophagy as underlying mechanism of neurodevelopmental disorders"

Neurodevelopmental disorders (NDDs) encompass a diverse array of conditions characterized by disruptions in central nervous system (CNS) development. A significant subset of NDDs, termed chromatinopathies, stem from mutations in genes responsible for epigenetic regulation, which modulate gene expression. Interestingly, a number of these chromatinopathy genes also govern the regulation of autophagy-related genes. These insights underscore the critical importance of tightly controlling the transcription of autophagy-related genes to manage autophagic activity. Autophagy, a highly conserved catabolic process, plays a pivotal role in maintaining cellular homeostasis and promoting survival by clearing cytosolic contents.. Leveraging genome-engineered and patient-derived stem cell models, we systematically investigated dysregulated autophagy as a potential shared underlying mechanism across different chromatinopathies. Our findings demonstrate that dysregulated autophagy contributes to neuronal and synaptic deficiencies observed in numerous chromatinopathies. This presents a promising avenue for advancing our understanding of disease pathology and, importantly, offers opportunities for the development of more targeted therapies for a broader spectrum of NDDs.

Prof. Dr. Nael Nadif Kasri
Department of Human Gentetics
Radboud University Medical Center