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Cell. Neurosci."],"abstract":"<jats:p>The glymphatic system theory introduces a new perspective on fluid flow and homeostasis in the brain. Here, cerebrospinal fluid and interstitial fluid (CSF-ISF) moves from the perivascular spaces (PVS) of arteries to those of veins for drainage. Aquaporin-4 (AQP4) plays a crucial role in driving fluid within the PVS. The impairment to AQP4 is closely linked to the dysfunction of the glymphatic system. The function of the glymphatic system is less active during waking but enhanced during sleep. The efficiency of the glymphatic system decreases with aging. Damage to the glymphatic system will give rise to the development and progression of many brain diseases, such as Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), chronic traumatic encephalopathy (CTE), and vascular dementia (VaD). Here, we reviewed previous research associated with the glymphatic system, including its concepts, principles, and influencing factors. We hypothesize that AQP4 could be a target for the prevention and treatment of certain brain diseases through the regulation on the glymphatic system.<\/jats:p>","DOI":"10.3389\/fncel.2025.1528995","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T02:28:58Z","timestamp":1739327338000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["Glymphatic system: a self-purification circulation in brain"],"prefix":"10.3389","volume":"19","author":[{"given":"Siying","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lini","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Xi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiying","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izmailova","family":"Regina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1007\/s00401-018-1812-4","article-title":"The role of brain barriers in fluid movement in the CNS: Is there a \u2018glymphatic\u2019system?","volume":"135","author":"Abbott","year":"2018","journal-title":"Acta Neuropathol."},{"key":"B2","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1093\/jnen\/nly065","article-title":"Lewy body pathology and chronic traumatic encephalopathy associated with contact sports.","volume":"77","author":"Adams","year":"2018","journal-title":"J. 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