Aquaporin-4 (AQP4) is the main water channel expressed primarily by astrocytes in the brain. AQP4 is highly polarized to astrocyte endfeet and facilitates the bidirectional transport of water within the blood-brain barrier (BBB), glial limitans, and the ventricles. AQP4 redistribution to the neuropil occurs in various neuropathological conditions including epilepsy, ischemia, multiple sclerosis (MS), and traumatic brain injury (TBI). Additionally, redistribution and upregulation of AQP4 around amyloid plaques occur in Alzheimer’s disease (AD). In recent years, the involvement of AQP4 in fluid exchange and specifically in the ‘glymphatic system’ concept, has been hotly debated. This system was described and named in 2013 as a waste disposal system in the vertebrate central nervous system.
Enrichment of AQP4 at specific subcellular sites requires a complex interaction between different AQP4 isoforms involved in macromolecular aggregation and the dystrophin-associated protein complex. Both extrinsic (e.g., damage to basement membranes) and intrinsic (e.g., changes in AQP4 isoform ratios or the anchoring proteins) can cause redistribution to the neuropil as observed in neurological diseases. AQP4 impacts neuron-glia signaling and is associated with abnormal neuronal activity and astrocyte plasticity. Although alterations in AQP4 expression and subcellular distribution have been widely recognized in various neuropathological states, neither the cellular mechanisms leading to altered AQP4 expression nor the consequences for disease pathophysiology are well understood. Our proposal aims to tackle questions such as:
Why is AQP4 so heavily enriched at specific subcellular sites?
Does the ‘glymphatic’ proposal make sense?
Is AQP4 redistribution protective or detrimental in the context of disease?
Can observations from genetic (e.g., knockout) studies be explained in terms of altered osmotic water transport?
Emerging studies dedicated to further understanding the pathological response of AQP4 in neurological diseases are key to identifying new therapeutic strategies.
This Research Topic aims to provide evidence of the cellular and molecular underpinnings involved in AQP4 dysregulation in order to expand our previous understanding of how AQP4 dysfunction impacts the symptomology and pathology of various neurological disorders. We welcome the submission of Original Research, Review, Mini-Review covering, but not limited to, the following themes:
• Identification of the cellular and molecular mechanisms that contribute to AQP4 redistribution
• Functional consequences for astrocyte physiology due to altered AQP4 distribution
• Understanding how AQP4 contributes to cell-cell signaling and disorders of water balance and osmoregulation
• Experimental studies that apply traditional and novel techniques to modulate AQP4
Aquaporin-4 (AQP4) is the main water channel expressed primarily by astrocytes in the brain. AQP4 is highly polarized to astrocyte endfeet and facilitates the bidirectional transport of water within the blood-brain barrier (BBB), glial limitans, and the ventricles. AQP4 redistribution to the neuropil occurs in various neuropathological conditions including epilepsy, ischemia, multiple sclerosis (MS), and traumatic brain injury (TBI). Additionally, redistribution and upregulation of AQP4 around amyloid plaques occur in Alzheimer’s disease (AD). In recent years, the involvement of AQP4 in fluid exchange and specifically in the ‘glymphatic system’ concept, has been hotly debated. This system was described and named in 2013 as a waste disposal system in the vertebrate central nervous system.
Enrichment of AQP4 at specific subcellular sites requires a complex interaction between different AQP4 isoforms involved in macromolecular aggregation and the dystrophin-associated protein complex. Both extrinsic (e.g., damage to basement membranes) and intrinsic (e.g., changes in AQP4 isoform ratios or the anchoring proteins) can cause redistribution to the neuropil as observed in neurological diseases. AQP4 impacts neuron-glia signaling and is associated with abnormal neuronal activity and astrocyte plasticity. Although alterations in AQP4 expression and subcellular distribution have been widely recognized in various neuropathological states, neither the cellular mechanisms leading to altered AQP4 expression nor the consequences for disease pathophysiology are well understood. Our proposal aims to tackle questions such as:
Why is AQP4 so heavily enriched at specific subcellular sites?
Does the ‘glymphatic’ proposal make sense?
Is AQP4 redistribution protective or detrimental in the context of disease?
Can observations from genetic (e.g., knockout) studies be explained in terms of altered osmotic water transport?
Emerging studies dedicated to further understanding the pathological response of AQP4 in neurological diseases are key to identifying new therapeutic strategies.
This Research Topic aims to provide evidence of the cellular and molecular underpinnings involved in AQP4 dysregulation in order to expand our previous understanding of how AQP4 dysfunction impacts the symptomology and pathology of various neurological disorders. We welcome the submission of Original Research, Review, Mini-Review covering, but not limited to, the following themes:
• Identification of the cellular and molecular mechanisms that contribute to AQP4 redistribution
• Functional consequences for astrocyte physiology due to altered AQP4 distribution
• Understanding how AQP4 contributes to cell-cell signaling and disorders of water balance and osmoregulation
• Experimental studies that apply traditional and novel techniques to modulate AQP4
