Piezo1 and Piezo2 in neurological disorders: From mechanotransduction to therapeutic potential

Mechanosensitive Piezo1 and Piezo2 channels convert mechanical forces into intracellular signals, playing essential roles in both physiological homeostasis and disease pathogenesis. This review synthesizes current evidence on their involvement in major neurological disorders, including stroke, Alzheimer's disease, traumatic brain injury, and glioma. Piezo1 primarily contributes to neuroinflammation, blood-brain barrier disruption, and tumor mechanosignaling, whereas Piezo2 dysfunction leads to sensory deficits, mechanical allodynia, and impaired proprioception. Notably, the functional consequences of Piezo activation are context-dependent: Piezo1 exacerbates ischemic brain damage but promotes amyloid-β clearance in Alzheimer's disease. Pharmacological modulators such as GsMTx4 and Yoda1 show promise in preclinical models, yet challenges remain regarding subtype selectivity and blood-brain barrier penetration. Targeting Piezo channels represents a promising therapeutic frontier, but success will require precise, cell-specific modulation based on disease stage and molecular context. This review highlights key pathogenic mechanisms, evaluates current pharmacological strategies, and outlines future directions for translating Piezo-targeted interventions into clinical practice.