Insights into the role of the mechanosensitive Piezo1 channel and signaling mechanisms in CNS functions and diseases

Abstract

The mechanosensitive Piezo1 channel is widely distributed in the central nervous system (CNS), expressed by neurons, astrocytes, oligodendrocytes, microglia, neural stem and progenitor cells, retinal ganglion and photoreceptor cells and, moreover, neurovascular and lymphatic endothelial cells, implicating an important role for the Piezo1 channel in the CNS physiology and disease. Indeed, recent studies have disclosed that the Piezo1 channel plays a vital part in mediating or modulating numerous CNS functions, ranging from brain development, synapse function, neurogenesis, axonal (re)generation, axonal pathfinding, astrocyte-neuron communication, axonal myelination, immune response, brain vasculature modelling to cerebrospinal fluid drainage. There is also increasing evidence to indicate critical engagement of the Piezo1 channel in the pathogenesis and progression of multiple debilitating CNS conditions, exemplified by spinal cord injury, stroke and related ischemia/reperfusion brain damage, neurodegenerative diseases, and age-related macular degeneration. Here, we provide a comprehensive overview of the current understanding and highlight the unanswered questions regarding the roles and mechanisms of the Piezo1 channel in CNS functions and diseases, presenting the Piezo1 channel as an attractive therapeutic target to intervene CNS damage and diseases.

Keywords: Diseases; Endothelial cells; Glia; Mechano-regulation; Neurons; Piezo1 channel.