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Allopregnanolone: Regenerative therapeutic to restore neurological health

Chronic stress has been proposed as a driver of altered brain structure and function, including the pathogenesis of neurodegenerative diseases and a driver of disease progression. A key outcome of stress in the brain is structural remodeling of neural architecture, which may be a sign of successful...

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Autores principales: Hernandez, Gerson D., Brinton, Roberta D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9755066/
https://www.ncbi.nlm.nih.gov/pubmed/36532370
http://dx.doi.org/10.1016/j.ynstr.2022.100502
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author Hernandez, Gerson D.
Brinton, Roberta D.
author_facet Hernandez, Gerson D.
Brinton, Roberta D.
author_sort Hernandez, Gerson D.
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description Chronic stress has been proposed as a driver of altered brain structure and function, including the pathogenesis of neurodegenerative diseases and a driver of disease progression. A key outcome of stress in the brain is structural remodeling of neural architecture, which may be a sign of successful adaptation, whereas persistence of these changes when stress ends indicate failed resilience. Neuroendocrine homeostasis and stress response are mainly dependent upon the functioning of the hypothalamic–pituitary–adrenal axis. Neurosteroids will fluctuate depending on whether the stress is acute or chronic. Advancements in neurosteroid research have led to the identification of multiple targets for drug development, but the most promising innovative target may be neurogenesis, given its potential impact in neurodegenerative disorders like Alzheimer's disease. Allopregnanolone is an endogenous pregnane neurosteroid and a reduced metabolite of progesterone, which acts as a potent allosteric modulator and direct activator of the GABA-chloride channel complex. Perhaps the most intriguing finding related to the potential therapeutic effects of allopregnanolone is its potential to promote neuroregeneration.
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spelling pubmed-97550662022-12-17 Allopregnanolone: Regenerative therapeutic to restore neurological health Hernandez, Gerson D. Brinton, Roberta D. Neurobiol Stress Article from the Special Issue dedicated to Dr. Bruce McEwen; Edited by Matthew N. Hill, Richard Hunter and Lawrence Reagan Chronic stress has been proposed as a driver of altered brain structure and function, including the pathogenesis of neurodegenerative diseases and a driver of disease progression. A key outcome of stress in the brain is structural remodeling of neural architecture, which may be a sign of successful adaptation, whereas persistence of these changes when stress ends indicate failed resilience. Neuroendocrine homeostasis and stress response are mainly dependent upon the functioning of the hypothalamic–pituitary–adrenal axis. Neurosteroids will fluctuate depending on whether the stress is acute or chronic. Advancements in neurosteroid research have led to the identification of multiple targets for drug development, but the most promising innovative target may be neurogenesis, given its potential impact in neurodegenerative disorders like Alzheimer's disease. Allopregnanolone is an endogenous pregnane neurosteroid and a reduced metabolite of progesterone, which acts as a potent allosteric modulator and direct activator of the GABA-chloride channel complex. Perhaps the most intriguing finding related to the potential therapeutic effects of allopregnanolone is its potential to promote neuroregeneration. Elsevier 2022-11-05 /pmc/articles/PMC9755066/ /pubmed/36532370 http://dx.doi.org/10.1016/j.ynstr.2022.100502 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article from the Special Issue dedicated to Dr. Bruce McEwen; Edited by Matthew N. Hill, Richard Hunter and Lawrence Reagan
Hernandez, Gerson D.
Brinton, Roberta D.
Allopregnanolone: Regenerative therapeutic to restore neurological health
title Allopregnanolone: Regenerative therapeutic to restore neurological health
title_full Allopregnanolone: Regenerative therapeutic to restore neurological health
title_fullStr Allopregnanolone: Regenerative therapeutic to restore neurological health
title_full_unstemmed Allopregnanolone: Regenerative therapeutic to restore neurological health
title_short Allopregnanolone: Regenerative therapeutic to restore neurological health
title_sort allopregnanolone: regenerative therapeutic to restore neurological health
topic Article from the Special Issue dedicated to Dr. Bruce McEwen; Edited by Matthew N. Hill, Richard Hunter and Lawrence Reagan
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9755066/
https://www.ncbi.nlm.nih.gov/pubmed/36532370
http://dx.doi.org/10.1016/j.ynstr.2022.100502
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