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Systemic Actions of SGLT2 Inhibition on Chronic mTOR Activation as a Shared Pathogenic Mechanism between Alzheimer’s Disease and Diabetes

Alzheimer’s disease (AD) affects tens of millions of people worldwide. Despite the advances in understanding the disease, there is an increased urgency for pharmacological approaches able of impacting its onset and progression. With a multifactorial nature, high incidence and prevalence in later yea...

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Autores principales: Stanciu, Gabriela Dumitrita, Rusu, Razvan Nicolae, Bild, Veronica, Filipiuc, Leontina Elena, Tamba, Bogdan-Ionel, Ababei, Daniela Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160780/
https://www.ncbi.nlm.nih.gov/pubmed/34069618
http://dx.doi.org/10.3390/biomedicines9050576
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author Stanciu, Gabriela Dumitrita
Rusu, Razvan Nicolae
Bild, Veronica
Filipiuc, Leontina Elena
Tamba, Bogdan-Ionel
Ababei, Daniela Carmen
author_facet Stanciu, Gabriela Dumitrita
Rusu, Razvan Nicolae
Bild, Veronica
Filipiuc, Leontina Elena
Tamba, Bogdan-Ionel
Ababei, Daniela Carmen
author_sort Stanciu, Gabriela Dumitrita
collection PubMed
description Alzheimer’s disease (AD) affects tens of millions of people worldwide. Despite the advances in understanding the disease, there is an increased urgency for pharmacological approaches able of impacting its onset and progression. With a multifactorial nature, high incidence and prevalence in later years of life, there is growing evidence highlighting a relationship between metabolic dysfunction related to diabetes and subject’s susceptibility to develop AD. The link seems so solid that sometimes AD and type 3 diabetes are used interchangeably. A candidate for a shared pathogenic mechanism linking these conditions is chronically-activated mechanistic target of rapamycin (mTOR). Chronic activation of unrestrained mTOR could be responsible for sustaining metabolic dysfunction that causes the breakdown of the blood-brain barrier, tau hyperphosphorylation and senile plaques formation in AD. It has been suggested that inhibition of sodium glucose cotransporter 2 (SGLT2) mediated by constant glucose loss, may restore mTOR cycle via nutrient-driven, preventing or even decreasing the AD progression. Currently, there is an unmet need for further research insight into molecular mechanisms that drive the onset and AD advancement as well as an increase in efforts to expand the testing of potential therapeutic strategies aimed to counteract disease progression in order to structure effective therapies.
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spelling pubmed-81607802021-05-29 Systemic Actions of SGLT2 Inhibition on Chronic mTOR Activation as a Shared Pathogenic Mechanism between Alzheimer’s Disease and Diabetes Stanciu, Gabriela Dumitrita Rusu, Razvan Nicolae Bild, Veronica Filipiuc, Leontina Elena Tamba, Bogdan-Ionel Ababei, Daniela Carmen Biomedicines Review Alzheimer’s disease (AD) affects tens of millions of people worldwide. Despite the advances in understanding the disease, there is an increased urgency for pharmacological approaches able of impacting its onset and progression. With a multifactorial nature, high incidence and prevalence in later years of life, there is growing evidence highlighting a relationship between metabolic dysfunction related to diabetes and subject’s susceptibility to develop AD. The link seems so solid that sometimes AD and type 3 diabetes are used interchangeably. A candidate for a shared pathogenic mechanism linking these conditions is chronically-activated mechanistic target of rapamycin (mTOR). Chronic activation of unrestrained mTOR could be responsible for sustaining metabolic dysfunction that causes the breakdown of the blood-brain barrier, tau hyperphosphorylation and senile plaques formation in AD. It has been suggested that inhibition of sodium glucose cotransporter 2 (SGLT2) mediated by constant glucose loss, may restore mTOR cycle via nutrient-driven, preventing or even decreasing the AD progression. Currently, there is an unmet need for further research insight into molecular mechanisms that drive the onset and AD advancement as well as an increase in efforts to expand the testing of potential therapeutic strategies aimed to counteract disease progression in order to structure effective therapies. MDPI 2021-05-19 /pmc/articles/PMC8160780/ /pubmed/34069618 http://dx.doi.org/10.3390/biomedicines9050576 Text en © 2021 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
Stanciu, Gabriela Dumitrita
Rusu, Razvan Nicolae
Bild, Veronica
Filipiuc, Leontina Elena
Tamba, Bogdan-Ionel
Ababei, Daniela Carmen
Systemic Actions of SGLT2 Inhibition on Chronic mTOR Activation as a Shared Pathogenic Mechanism between Alzheimer’s Disease and Diabetes
title Systemic Actions of SGLT2 Inhibition on Chronic mTOR Activation as a Shared Pathogenic Mechanism between Alzheimer’s Disease and Diabetes
title_full Systemic Actions of SGLT2 Inhibition on Chronic mTOR Activation as a Shared Pathogenic Mechanism between Alzheimer’s Disease and Diabetes
title_fullStr Systemic Actions of SGLT2 Inhibition on Chronic mTOR Activation as a Shared Pathogenic Mechanism between Alzheimer’s Disease and Diabetes
title_full_unstemmed Systemic Actions of SGLT2 Inhibition on Chronic mTOR Activation as a Shared Pathogenic Mechanism between Alzheimer’s Disease and Diabetes
title_short Systemic Actions of SGLT2 Inhibition on Chronic mTOR Activation as a Shared Pathogenic Mechanism between Alzheimer’s Disease and Diabetes
title_sort systemic actions of sglt2 inhibition on chronic mtor activation as a shared pathogenic mechanism between alzheimer’s disease and diabetes
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160780/
https://www.ncbi.nlm.nih.gov/pubmed/34069618
http://dx.doi.org/10.3390/biomedicines9050576
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