Diverse roles of connexins in the neuro-vasculature in homeostasis and disease

Significant progress has advanced our understanding of brain physiology. The brain is now recognized as an integrated network rather than a compartmentalized organ, composed of diverse cell types including neurons, glial cells, and vascular components. Communication within this neurovascular unit relies on multiple receptors, transporters, and channels. Among these, gap junction channels formed by connexin proteins play a central role by enabling direct intercellular exchange of ions, metabolites, and signaling molecules. In the healthy brain, connexins contribute to homeostatic balance and neuronal activity, whereas their dysregulation has been implicated in the pathogenesis of multiple neurological disorders. In this review, we summarize current knowledge on the physiological roles of connexins in the brain, analyze evidence from preclinical and clinical studies linking connexin dysfunction to disease, and discuss emerging therapeutic strategies targeting connexin-mediated signaling for the treatment of brain disorders.