Research Evidence of the Role of the Glymphatic System and Its Potential Pharmacological Modulation in Neurodegenerative Diseases
dc.contributor.author | Verghese, JP | |
dc.contributor.author | Terry, A | |
dc.contributor.author | de Natale, ER | |
dc.contributor.author | Politis, M | |
dc.date.accessioned | 2022-12-15T14:08:55Z | |
dc.date.issued | 2022-11-25 | |
dc.date.updated | 2022-12-15T13:49:12Z | |
dc.description.abstract | The glymphatic system is a unique pathway that utilises end-feet Aquaporin 4 (AQP4) channels within perivascular astrocytes, which is believed to cause cerebrospinal fluid (CSF) inflow into perivascular space (PVS), providing nutrients and waste disposal of the brain parenchyma. It is theorised that the bulk flow of CSF within the PVS removes waste products, soluble proteins, and products of metabolic activity, such as amyloid-β (Aβ). In the experimental model, the glymphatic system is selectively active during slow-wave sleep, and its activity is affected by both sleep dysfunction and deprivation. Dysfunction of the glymphatic system has been proposed as a potential key driver of neurodegeneration. This hypothesis is indirectly supported by the close relationship between neurodegenerative diseases and sleep alterations, frequently occurring years before the clinical diagnosis. Therefore, a detailed characterisation of the function of the glymphatic system in human physiology and disease would shed light on its early stage pathophysiology. The study of the glymphatic system is also critical to identifying means for its pharmacological modulation, which may have the potential for disease modification. This review will critically outline the primary evidence from literature about the dysfunction of the glymphatic system in neurodegeneration and discuss the rationale and current knowledge about pharmacological modulation of the glymphatic system in the animal model and its potential clinical applications in human clinical trials. | en_GB |
dc.format.extent | 6964- | |
dc.format.medium | Electronic | |
dc.identifier.citation | Vol. 11(23), article 6964 | en_GB |
dc.identifier.doi | https://doi.org/10.3390/jcm11236964 | |
dc.identifier.uri | http://hdl.handle.net/10871/132038 | |
dc.language.iso | en | en_GB |
dc.publisher | MDPI | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/36498538 | en_GB |
dc.rights | © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). | en_GB |
dc.subject | APQ4 | en_GB |
dc.subject | Alzheimer’s disease | en_GB |
dc.subject | Huntington’s disease | en_GB |
dc.subject | Parkinson’s disease | en_GB |
dc.subject | glymphatics system | en_GB |
dc.subject | idiopathic normal pressure hydrocephalus | en_GB |
dc.subject | motor neurone disease | en_GB |
dc.subject | multiple sclerosis | en_GB |
dc.subject | neurodegeneration | en_GB |
dc.subject | pharmacological modulation | en_GB |
dc.title | Research Evidence of the Role of the Glymphatic System and Its Potential Pharmacological Modulation in Neurodegenerative Diseases | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2022-12-15T14:08:55Z | |
exeter.place-of-publication | Switzerland | |
dc.description | This is the final version. Available on open access from MDPI via the DOI in this record | en_GB |
dc.identifier.eissn | 2077-0383 | |
dc.identifier.journal | Journal of Clinical Medicine | en_GB |
dc.relation.ispartof | J Clin Med, 11(23) | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2022-11-24 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2022-11-25 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2022-12-15T14:07:16Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2022-12-15T14:08:58Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2022-11-25 |
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Except where otherwise noted, this item's licence is described as © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).