The potential roles of aquaporin 4 in amyotrophic lateral sclerosis

  • Shuang Zou
  • Yu-Long Lan
  • Hongjin Wang
  • Bo ZhangEmail author
  • Yan-Guo SunEmail author
Review Article


Aquaporin 4 (AQP4) is a primary water channel found on astrocytes in the central nervous system (CNS). Besides its function in water and ion homeostasis, AQP4 has also been documented to be involved in a myriad of acute and chronic cerebral pathologies, including autoimmune neurodegenerative diseases. AQP4 has been postulated to be associated with the incidence of a progressive neurodegenerative disorder known as amyotrophic lateral sclerosis (ALS), a disease that targets the motor neurons, causing muscle weakness and eventually paralysis. Raised AQP4 levels were noted in association with vessels surrounded with swollen astrocytic processes as well as in the brainstem, cortex, and gray matter in patients with terminal ALS. AQP4 depolarization may lead to motor neuron degeneration in ALS via GLT-1. Besides, alterations in AQP4 expression in ALS may result in the loss of blood–brain barrier (BBB) integrity. Changes in AQP4 function may also disrupt K+ homeostasis and cause connexin dysregulation, the latter of which is associated to ALS disease progression. Furthermore, AQP4 suppression augments recovery in motor function in ALS, a phenomenon thought to be associated to NGF. No therapeutic drug targeting AQP4 has been developed to date. Nevertheless, the plethora of suggestive experimental results underscores the significance of further exploration into this area.


AQP4 Amyotrophic lateral sclerosis Target Therapy 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical standards

This article does not contain any study with human subjects performed by any of the authors.


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Copyright information

© Fondazione Società Italiana di Neurologia 2019

Authors and Affiliations

  1. 1.Computer CenterThe Second Affiliated Hospital of Dalian Medical UniversityDalianChina
  2. 2.Department of NeurosurgeryThe Second Affiliated Hospital of Dalian Medical UniversityDalianChina
  3. 3.Department of NeurologyThe Second Affiliated Hospital of Dalian Medical UniversityDalianChina
  4. 4.Department of PhysiologyDalian Medical UniversityDalianChina
  5. 5.Department of NeurosurgeryShenzhen People’s HospitalShenzhenChina

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