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Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia

The swift rise in acceptance of molecular principles defining phase separation by a broad array of scientific disciplines is shadowed by increasing discoveries linking phase separation to pathological aggregations associated with numerous neurodegenerative disorders, including Alzheimer’s disease, t...

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Autores principales: Loh, Doris, Reiter, Russel J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10054283/
https://www.ncbi.nlm.nih.gov/pubmed/36982909
http://dx.doi.org/10.3390/ijms24065835
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author Loh, Doris
Reiter, Russel J.
author_facet Loh, Doris
Reiter, Russel J.
author_sort Loh, Doris
collection PubMed
description The swift rise in acceptance of molecular principles defining phase separation by a broad array of scientific disciplines is shadowed by increasing discoveries linking phase separation to pathological aggregations associated with numerous neurodegenerative disorders, including Alzheimer’s disease, that contribute to dementia. Phase separation is powered by multivalent macromolecular interactions. Importantly, the release of water molecules from protein hydration shells into bulk creates entropic gains that promote phase separation and the subsequent generation of insoluble cytotoxic aggregates that drive healthy brain cells into diseased states. Higher viscosity in interfacial waters and limited hydration in interiors of biomolecular condensates facilitate phase separation. Light, water, and melatonin constitute an ancient synergy that ensures adequate protein hydration to prevent aberrant phase separation. The 670 nm visible red wavelength found in sunlight and employed in photobiomodulation reduces interfacial and mitochondrial matrix viscosity to enhance ATP production via increasing ATP synthase motor efficiency. Melatonin is a potent antioxidant that lowers viscosity to increase ATP by scavenging excess reactive oxygen species and free radicals. Reduced viscosity by light and melatonin elevates the availability of free water molecules that allow melatonin to adopt favorable conformations that enhance intrinsic features, including binding interactions with adenosine that reinforces the adenosine moiety effect of ATP responsible for preventing water removal that causes hydrophobic collapse and aggregation in phase separation. Precise recalibration of interspecies melatonin dosages that account for differences in metabolic rates and bioavailability will ensure the efficacious reinstatement of the once-powerful ancient synergy between light, water, and melatonin in a modern world.
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spelling pubmed-100542832023-03-30 Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia Loh, Doris Reiter, Russel J. Int J Mol Sci Review The swift rise in acceptance of molecular principles defining phase separation by a broad array of scientific disciplines is shadowed by increasing discoveries linking phase separation to pathological aggregations associated with numerous neurodegenerative disorders, including Alzheimer’s disease, that contribute to dementia. Phase separation is powered by multivalent macromolecular interactions. Importantly, the release of water molecules from protein hydration shells into bulk creates entropic gains that promote phase separation and the subsequent generation of insoluble cytotoxic aggregates that drive healthy brain cells into diseased states. Higher viscosity in interfacial waters and limited hydration in interiors of biomolecular condensates facilitate phase separation. Light, water, and melatonin constitute an ancient synergy that ensures adequate protein hydration to prevent aberrant phase separation. The 670 nm visible red wavelength found in sunlight and employed in photobiomodulation reduces interfacial and mitochondrial matrix viscosity to enhance ATP production via increasing ATP synthase motor efficiency. Melatonin is a potent antioxidant that lowers viscosity to increase ATP by scavenging excess reactive oxygen species and free radicals. Reduced viscosity by light and melatonin elevates the availability of free water molecules that allow melatonin to adopt favorable conformations that enhance intrinsic features, including binding interactions with adenosine that reinforces the adenosine moiety effect of ATP responsible for preventing water removal that causes hydrophobic collapse and aggregation in phase separation. Precise recalibration of interspecies melatonin dosages that account for differences in metabolic rates and bioavailability will ensure the efficacious reinstatement of the once-powerful ancient synergy between light, water, and melatonin in a modern world. MDPI 2023-03-19 /pmc/articles/PMC10054283/ /pubmed/36982909 http://dx.doi.org/10.3390/ijms24065835 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Review
Loh, Doris
Reiter, Russel J.
Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia
title Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia
title_full Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia
title_fullStr Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia
title_full_unstemmed Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia
title_short Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia
title_sort light, water, and melatonin: the synergistic regulation of phase separation in dementia
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10054283/
https://www.ncbi.nlm.nih.gov/pubmed/36982909
http://dx.doi.org/10.3390/ijms24065835
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