Harnessing metabolic control for synaptic stability: REST/NRSF links glycolytic inhibition to excitatory neurotransmission.

ABSTRACT: Under resting conditions most neuronal ATP is produced through mitochondrial oxidative phosphorylation, whereas glycolysis becomes more important during intense neuronal firing. Recent studies suggest that inhibiting glycolysis plays a key role in regulating seizure-related hyperactivity, with the epigenetic modulator REST/NRSF being activated when glycolysis inhibition lowers the NADH/NAD⁺ ratio. Our previous research has shown that REST/NRSF initiates homeostatic processes to counteract neuronal hyperactivity by regulating both firing and synaptic activities. However, the exact mechanism through which the metabolic activation of REST/NRSF controls neuronal excitability is still unknown. Here, we studied the role of REST/NRSF in the effects of glycolysis inhibition on hippocamp

SUBMITTER: Ferrante D 

PROVIDER: S-EPMC12645552 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature