Dysregulated Expression of Canonical and Non-Canonical Glycolytic Enzyme Isoforms in Peripheral Blood from Subjects...

Glycolysis is primarily involved in ATP production but also modulates oxidative stress. Chronic alcohol consumption is correlated with an increased incidence of multiple diseases, including cancer and neurodegenerative diseases (NDDs), though the underlying mechanisms remain unclear. Guided by a literature review and bioinformatics analysis, we evaluated the expression of 22 genes encoding various isoforms of seven glycolytic enzymes (GEs) in the peripheral blood of patients with alcohol use disorder (AUD), individuals with acute alcohol consumption (AAC), and their respective control groups using qPCR. In parallel, we evaluated the expression of selected genes coding for GEs linked to NDDs, as well as astrocytic markers in primary mouse astrocyte cultures exposed to ethanol. Thirteen GE-related genes, including non-canonical isoforms, were significantly dysregulated in AUD patients; notably, eight of these genes showed similar alterations in individuals with AAC. Several enzymes encoded by these genes are known to be regulated by oxidative stress. Ethanol-exposed astrocytes also showed altered expression of glycolytic genes associated with NDDs and astrocyte function. These findings indicate that glycolytic dysregulation is driven by ethanol intake, regardless of exposure duration or organic damage, highlighting a link between ethanol-driven redox imbalance and glycolytic remodeling, which could contribute to organ damage.