biostudies-literatureUnknownAngireddy RNCATS NIH HHSNINDS NIH HHSNCI NIH HHS<h4>Background and objectives</h4>TBCK syndrome is a rare fatal pediatric neurodegenerative disease caused by biallelic loss-of-function mutations in the <i>TBCK</i> gene. Previous studies by our lab and others have implicated mTOR, autophagy, lysosomes, and intracellular mRNA transport, however the exact primary pathologic mechanism is unknown. This gap has prevented the development of targeted therapies.<h4>Methods</h4>We employed a human neural progenitor cell line (NPC), ReNcell VM, which can differentiate into neurons and astrocytes, to understand the role of TBCK in mTORC1 activity and neuronal autophagy and cellular mechanisms of pathology. We used shRNA technology to knockdown TBCK in ReNcells.<h4>Results</h4>These data showed that loss of TBCK did not inhibit mTORC1 activity in nebioRxiv : the preprint server for biology2024.10.30.621078https://www.ebi.ac.uk/biostudies/studies/S-EPMC11565812biostudies-literatureA Novel Human TBCK- Neuronal Cell Model Results in Severe Neurodegeneration and Partial Rescue with Mitochondrial Fission Inhibition.PMC11565812R50 CA211199K08 NS109281KL2 TR001879Diaz AMurali SBhoj EJKSmith SOhl LClark KKarisetty BCKatsura KAAngireddy RKossenkov AVfalseA Novel Human TBCK- Neuronal Cell Model Results in Severe Neurodegeneration and Partial Rescue with Mitochondrial Fission Inhibition.<h4>Background and objectives</h4>TBCK syndrome is a rare fatal pediatric neurodegenerative disease caused by biallelic loss-of-function mutations in the <i>TBCK</i> gene. Previous studies by our lab and others have implicated mTOR, autophagy, lysosomes, and intracellular mRNA transport, however the exact primary pathologic mechanism is unknown. This gap has prevented the development of targeted therapies.<h4>Methods</h4>We employed a human neural progenitor cell line (NPC), ReNcell VM, which can differentiate into neurons and astrocytes, to understand the role of TBCK in mTORC1 activity and neuronal autophagy and cellular mechanisms of pathology. We used shRNA technology to knockdown TBCK in ReNcells.<h4>Results</h4>These data showed that loss of TBCK did not inhibit mTORC1 activity in ne2024-01-01T00:00:00Z2024 Oct2026-04-08T19:23:52.537Z2025-04-21T21:47:45.258ZS-EPMC115658123955398510.1101/2024.10.30.621078