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Glymphatic system, AQP4, and their implications in Alzheimer's disease

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SPRINGERNATURE
DOI: 10.1186/s42466-021-00102-7

关键词

Glymphatic system; Alzheimer's disease; Aquaporin-4; Amyloid-beta; Clearance

资金

  1. Integrated Programme of SRamp
  2. TDpAGE [CENTRO-01-0145-FEDER-000003]

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This article discusses the alternative clearance systems required by the central nervous system in the absence of a conventional lymphatic system. It highlights the importance of the glymphatic system and AQP4 in Alzheimer's disease, as well as the impact of AQP4 mislocalisation on disease progression.
Lacking conventional lymphatic system, the central nervous system requires alternative clearance systems, such as the glymphatic system, which promotes clearance of interstitial solutes. Aquaporin-4 water channels (AQP4) are an integral part of this system and related to neuropathologies, such as Alzheimer's disease (AD). The clearance of Alzheimer's associated proteins amyloid beta and tau is diminished by glymphatic system impairment, due to lack of AQP4. Even though AQP4 mislocalisation (which affects its activity) is a phenotype of AD, it remains a controversial topic, as it is still unclear if it is a phenotype-promoting factor or a consequence of this pathology. This review provides important and updated knowledge about glymphatic system, AQP4 itself, and their link with Alzheimer's disease. Finally, AQP4 as a therapeutic target is proposed to ameliorate Alzheimer's Disease and other neuropathologies AQP4-related.

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