Differential response of C9orf72 transcripts following neuronal depolarization.

ABSTRACT: The (G₄C₂)_n nucleotide repeat expansion (NRE) mutation in C9orf72 is the most common genetic cause of ALS and FTD. The biological functions of C9orf72 are becoming understood, but it is unclear if this gene is regulated in a neural-specific manner. Neuronal activity is a crucial modifier of biological processes in health and neurodegenerative disease contexts. Here, we show that prolonged membrane depolarization in healthy human iPSC-cortical neurons leads to a significant downregulation of a transcript variant 3 (V3) of C9orf72, with a concomitant increase in variant 2 (V2), which leads to total C9orf72 RNA transcript levels remaining unchanged. However, the same response is not observed in cortical neurons derived from patients with the C9-NRE mutation. T

SUBMITTER: Ghaffari LT 

PROVIDER: S-EPMC10272498 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature