Aquaporin-1 in peripheral nerve physiology and pathology: implications for uremic peripheral neuropathy

Aquaporin-1 (AQP1) is a well-characterized transmembrane water channel widely expressed in the peripheral nervous system (PNS), where it contributes to water balance and regulation of the local neural microenvironment. Beyond its classical role in water transport, AQP1 has been implicated in edema formation, Schwann cell activity, nociceptive signaling, and inflammatory responses. However, these findings derive largely from experimental settings and vary in consistency across different models. Direct evidence supporting a role for AQP1 in uremic peripheral neuropathy (UPN) is currently lacking. This review re-examines the relevance of AQP1 in the PNS by integrating structural, cellular, and functional evidence, and evaluating how far current observations can be extended to the UPN context.

We synthesized available literature on AQP1 in peripheral nerve biology, with particular attention to non-uremic models including nerve injury, hypoxia, osmotic stress, and inflammation. The applicability of these mechanistic clues to the complex metabolic, toxic, and inflammatory environment of uremia was critically assessed.

Alterations in AQP1 expression or function may plausibly contribute to peripheral nerve dysfunction under uremic conditions, potentially involving disrupted water homeostasis, Schwann cell instability, and altered neuroimmune interactions. However, these assumptions remain speculative. Existing models do not fully reproduce the uremic milieu, and no direct experimental validation in UPN is currently available.

Current knowledge on AQP1 in UPN remains fragmented, necessitating a clearer distinction between established findings and hypothesis-driven interpretations. Further studies in uremia-specific animal models and clinical cohorts will be essential to clarify the pathophysiological and therapeutic significance of AQP1 in this condition.