A Novel Human TBCK- Neuronal Cell Model Results in Severe Neurodegeneration and Partial Rescue with Mitochondrial Fission Inhibition.

ABSTRACT:

Background and objectives

TBCK syndrome is a rare fatal pediatric neurodegenerative disease caused by biallelic loss-of-function mutations in the TBCK 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.

Methods

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.

Results

These data showed that loss of TBCK did not inhibit mTORC1 activity in ne

SUBMITTER: Angireddy R 

PROVIDER: S-EPMC11565812 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature