High glucose induces tau hyperphosphorylation in hippocampal neurons via inhibition of ALKBH5-mediated Dgkh m⁶A demethylation: a potential mechanism for diabetic cognitive dysfunction.

ABSTRACT: Tau hyperphosphorylation in hippocampal neurons has an important pathogenetic role in the development of diabetic cognitive dysfunction. N⁶-methyladenosine (m⁶A) methylation is the most common modification of eukaryotic mRNA and is involved in regulating diverse biological processes. However, the role of m⁶A alteration in tau hyperphosphorylation of hippocampus neurons has not been reported. We found lower ALKBH5 expression in the hippocampus of diabetic rats and in HN-h cells with high-glucose intervention, accompanied by tau hyperphosphorylation. ALKBH5 overexpression significantly reversed tau hyperphosphorylation in high-glucose-stimulated HN-h cells. Furthermore, we found and confirmed by m⁶A-mRNA epitope transcriptome microarray and transcr

SUBMITTER: Qu M 

PROVIDER: S-EPMC10310746 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature