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Alzheimer’s disease as a chronic maladaptive polyamine stress response

Polyamines are nitrogen-rich polycationic ubiquitous bioactive molecules with diverse evolutionary-conserved functions. Their activity interferes with numerous genes' expression resulting in cell proliferation and signaling modulation. The intracellular levels of polyamines are precisely contro...

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Detalles Bibliográficos
Autores principales: Polis, Baruh, Karasik, David, Samson, Abraham O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064158/
https://www.ncbi.nlm.nih.gov/pubmed/33811757
http://dx.doi.org/10.18632/aging.202928
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author Polis, Baruh
Karasik, David
Samson, Abraham O.
author_facet Polis, Baruh
Karasik, David
Samson, Abraham O.
author_sort Polis, Baruh
collection PubMed
description Polyamines are nitrogen-rich polycationic ubiquitous bioactive molecules with diverse evolutionary-conserved functions. Their activity interferes with numerous genes' expression resulting in cell proliferation and signaling modulation. The intracellular levels of polyamines are precisely controlled by an evolutionary-conserved machinery. Their transient synthesis is induced by heat stress, radiation, and other traumatic stimuli in a process termed the polyamine stress response (PSR). Notably, polyamine levels decline gradually with age; and external supplementation improves lifespan in model organisms. This corresponds to cytoprotective and reactive oxygen species scavenging properties of polyamines. Paradoxically, age-associated neurodegenerative disorders are characterized by upsurge in polyamines levels, indicating polyamine pleiotropic, adaptive, and pathogenic roles. Specifically, arginase overactivation and arginine brain deprivation have been shown to play an important role in Alzheimer’s disease (AD) pathogenesis. Here, we assert that a universal short-term PSR associated with acute stimuli is beneficial for survival. However, it becomes detrimental and maladaptive following chronic noxious stimuli, especially in an aging organism. Furthermore, we regard cellular senescence as an adaptive response to stress and suggest that PSR plays a central role in age-related neurodegenerative diseases' pathogenesis. Our perspective on AD proposes an inclusive reassessment of the causal relationships between the classical hallmarks and clinical manifestation. Consequently, we offer a novel treatment strategy predicated upon this view and suggest fine-tuning of arginase activity with natural inhibitors to preclude or halt the development of AD-related dementia.
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spelling pubmed-80641582021-04-26 Alzheimer’s disease as a chronic maladaptive polyamine stress response Polis, Baruh Karasik, David Samson, Abraham O. Aging (Albany NY) Review Polyamines are nitrogen-rich polycationic ubiquitous bioactive molecules with diverse evolutionary-conserved functions. Their activity interferes with numerous genes' expression resulting in cell proliferation and signaling modulation. The intracellular levels of polyamines are precisely controlled by an evolutionary-conserved machinery. Their transient synthesis is induced by heat stress, radiation, and other traumatic stimuli in a process termed the polyamine stress response (PSR). Notably, polyamine levels decline gradually with age; and external supplementation improves lifespan in model organisms. This corresponds to cytoprotective and reactive oxygen species scavenging properties of polyamines. Paradoxically, age-associated neurodegenerative disorders are characterized by upsurge in polyamines levels, indicating polyamine pleiotropic, adaptive, and pathogenic roles. Specifically, arginase overactivation and arginine brain deprivation have been shown to play an important role in Alzheimer’s disease (AD) pathogenesis. Here, we assert that a universal short-term PSR associated with acute stimuli is beneficial for survival. However, it becomes detrimental and maladaptive following chronic noxious stimuli, especially in an aging organism. Furthermore, we regard cellular senescence as an adaptive response to stress and suggest that PSR plays a central role in age-related neurodegenerative diseases' pathogenesis. Our perspective on AD proposes an inclusive reassessment of the causal relationships between the classical hallmarks and clinical manifestation. Consequently, we offer a novel treatment strategy predicated upon this view and suggest fine-tuning of arginase activity with natural inhibitors to preclude or halt the development of AD-related dementia. Impact Journals 2021-04-03 /pmc/articles/PMC8064158/ /pubmed/33811757 http://dx.doi.org/10.18632/aging.202928 Text en Copyright: © 2021 Polis et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Review
Polis, Baruh
Karasik, David
Samson, Abraham O.
Alzheimer’s disease as a chronic maladaptive polyamine stress response
title Alzheimer’s disease as a chronic maladaptive polyamine stress response
title_full Alzheimer’s disease as a chronic maladaptive polyamine stress response
title_fullStr Alzheimer’s disease as a chronic maladaptive polyamine stress response
title_full_unstemmed Alzheimer’s disease as a chronic maladaptive polyamine stress response
title_short Alzheimer’s disease as a chronic maladaptive polyamine stress response
title_sort alzheimer’s disease as a chronic maladaptive polyamine stress response
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064158/
https://www.ncbi.nlm.nih.gov/pubmed/33811757
http://dx.doi.org/10.18632/aging.202928
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