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Altered sleep and neurovascular dysfunction in alpha-synucleinopathies: the perfect storm for glymphatic failure
Clinical and cognitive progression in alpha-synucleinopathies is highly heterogeneous. While some patients remain stable over long periods of time, other suffer early dementia or fast motor deterioration. Sleep disturbances and nocturnal blood pressure abnormalities have been identified as independe...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10484002/ https://www.ncbi.nlm.nih.gov/pubmed/37693650 http://dx.doi.org/10.3389/fnagi.2023.1251755 |
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author | Buongiorno, Mariateresa Marzal, Clara Fernandez, Manel Cullell, Natalia de Mena, Lorena Sánchez-Benavides, Gonzalo de la Sierra, Alejandro Krupinski, Jerzy Compta, Yaroslau |
author_facet | Buongiorno, Mariateresa Marzal, Clara Fernandez, Manel Cullell, Natalia de Mena, Lorena Sánchez-Benavides, Gonzalo de la Sierra, Alejandro Krupinski, Jerzy Compta, Yaroslau |
author_sort | Buongiorno, Mariateresa |
collection | PubMed |
description | Clinical and cognitive progression in alpha-synucleinopathies is highly heterogeneous. While some patients remain stable over long periods of time, other suffer early dementia or fast motor deterioration. Sleep disturbances and nocturnal blood pressure abnormalities have been identified as independent risk factors for clinical progression but a mechanistic explanation linking both aspects is lacking. We hypothesize that impaired glymphatic system might play a key role on clinical progression. Glymphatic system clears brain waste during specific sleep stages, being blood pressure the motive force that propels the interstitial fluid through brain tissue to remove protein waste. Thus, the combination of severe sleep alterations, such as REM sleep behavioral disorder, and lack of the physiological nocturnal decrease of blood pressure due to severe dysautonomia may constitute the perfect storm for glymphatic failure, causing increased abnormal protein aggregation and spreading. In Lewy body disorders (Parkinson’s disease and dementia with Lewy bodies) the increment of intraneuronal alpha-synuclein and extracellular amyloid-β would lead to cognitive deterioration, while in multisystemic atrophy, increased pathology in oligodendroglia would relate to the faster and malignant motor progression. We present a research model that may help in developing studies aiming to elucidate the role of glymphatic function and associated factors mainly in alpha-synucleinopathies, but that could be relevant also for other protein accumulation-related neurodegenerative diseases. If the model is proven to be useful could open new lines for treatments targeting glymphatic function (for example through control of nocturnal blood pressure) with the objective to ameliorate cognitive and motor progression in alpha-synucleinopathies. |
format | Online Article Text |
id | pubmed-10484002 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-104840022023-09-08 Altered sleep and neurovascular dysfunction in alpha-synucleinopathies: the perfect storm for glymphatic failure Buongiorno, Mariateresa Marzal, Clara Fernandez, Manel Cullell, Natalia de Mena, Lorena Sánchez-Benavides, Gonzalo de la Sierra, Alejandro Krupinski, Jerzy Compta, Yaroslau Front Aging Neurosci Neuroscience Clinical and cognitive progression in alpha-synucleinopathies is highly heterogeneous. While some patients remain stable over long periods of time, other suffer early dementia or fast motor deterioration. Sleep disturbances and nocturnal blood pressure abnormalities have been identified as independent risk factors for clinical progression but a mechanistic explanation linking both aspects is lacking. We hypothesize that impaired glymphatic system might play a key role on clinical progression. Glymphatic system clears brain waste during specific sleep stages, being blood pressure the motive force that propels the interstitial fluid through brain tissue to remove protein waste. Thus, the combination of severe sleep alterations, such as REM sleep behavioral disorder, and lack of the physiological nocturnal decrease of blood pressure due to severe dysautonomia may constitute the perfect storm for glymphatic failure, causing increased abnormal protein aggregation and spreading. In Lewy body disorders (Parkinson’s disease and dementia with Lewy bodies) the increment of intraneuronal alpha-synuclein and extracellular amyloid-β would lead to cognitive deterioration, while in multisystemic atrophy, increased pathology in oligodendroglia would relate to the faster and malignant motor progression. We present a research model that may help in developing studies aiming to elucidate the role of glymphatic function and associated factors mainly in alpha-synucleinopathies, but that could be relevant also for other protein accumulation-related neurodegenerative diseases. If the model is proven to be useful could open new lines for treatments targeting glymphatic function (for example through control of nocturnal blood pressure) with the objective to ameliorate cognitive and motor progression in alpha-synucleinopathies. Frontiers Media S.A. 2023-08-24 /pmc/articles/PMC10484002/ /pubmed/37693650 http://dx.doi.org/10.3389/fnagi.2023.1251755 Text en Copyright © 2023 Buongiorno, Marzal, Fernandez, Cullell, de Mena, Sánchez-Benavides, de la Sierra, Krupinski and Compta. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Buongiorno, Mariateresa Marzal, Clara Fernandez, Manel Cullell, Natalia de Mena, Lorena Sánchez-Benavides, Gonzalo de la Sierra, Alejandro Krupinski, Jerzy Compta, Yaroslau Altered sleep and neurovascular dysfunction in alpha-synucleinopathies: the perfect storm for glymphatic failure |
title | Altered sleep and neurovascular dysfunction in alpha-synucleinopathies: the perfect storm for glymphatic failure |
title_full | Altered sleep and neurovascular dysfunction in alpha-synucleinopathies: the perfect storm for glymphatic failure |
title_fullStr | Altered sleep and neurovascular dysfunction in alpha-synucleinopathies: the perfect storm for glymphatic failure |
title_full_unstemmed | Altered sleep and neurovascular dysfunction in alpha-synucleinopathies: the perfect storm for glymphatic failure |
title_short | Altered sleep and neurovascular dysfunction in alpha-synucleinopathies: the perfect storm for glymphatic failure |
title_sort | altered sleep and neurovascular dysfunction in alpha-synucleinopathies: the perfect storm for glymphatic failure |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10484002/ https://www.ncbi.nlm.nih.gov/pubmed/37693650 http://dx.doi.org/10.3389/fnagi.2023.1251755 |
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