ZBTB7A-mediated regulation of astrocytic glycolysis in neurodegenerative diseases: insights from literature review and bioinformatics prediction.

The incidence of neurodegenerative diseases, including Alzheimer's disease (AD), continues to increase with the extension of human lifespan. However, their pathogenesis remains incompletely understood. Altered energy metabolism, particularly glucose metabolism involving glycolysis and oxidative phosphorylation, is widely recognized as an early pathological feature of neurodegenerative diseases. Astrocytes, the most numerous and widely distributed functional cells in the central nervous system (CNS), support neuronal energy demands through the astrocyte-neuronal lactate shuttle (ANLS). Glycolysis is a major pathway of astrocyte energy metabolism, and enhanced astrocytic glucose uptake and glycolytic flux may help attenuate the progression of neurodegenerative diseases such as AD. Zinc Finger and BTB Domain Containing 7A (ZBTB7A) is a POZ/BTB and Krüppel (POK) family transcription factor that has been implicated in the regulation of metabolic genes, including glycolysis-related genes, in several cellular contexts. However, its role in astrocyte glycolytic regulation under neurodegenerative conditions remains unclear. In this review, we summarize current knowledge of ZBTB7A biology, astrocyte glycolysis, and glial metabolic dysfunction in neurodegenerative diseases, and integrate published evidence with bioinformatics-based transcription factor binding prediction. Our analysis identified putative ZBTB7A-binding motifs in promoter regions of genes involved in glucose uptake, glycolytic flux, lactate production, and lactate transport. These findings suggest a potential association between ZBTB7A and the astrocytic glycolytic/lactate metabolic network. Therefore, this review provides a conceptual basis for future studies on ZBTB7A-associated transcriptional regulation in astrocyte metabolic remodeling and its potential relevance to neurodegenerative diseases.