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The Strategies for Treating “Alzheimer’s Disease”: Insulin Signaling May Be a Feasible Target

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by senile plaques formed by amyloid-beta (Aβ) extracellularly and neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau protein intracellularly. Apart from these two features, insulin deficiency and insulin resistance...

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Autores principales: You, Guanying, Yao, Jinyi, Liu, Qiong, Li, Nan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777526/
https://www.ncbi.nlm.nih.gov/pubmed/36547082
http://dx.doi.org/10.3390/cimb44120421
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author You, Guanying
Yao, Jinyi
Liu, Qiong
Li, Nan
author_facet You, Guanying
Yao, Jinyi
Liu, Qiong
Li, Nan
author_sort You, Guanying
collection PubMed
description Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by senile plaques formed by amyloid-beta (Aβ) extracellularly and neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau protein intracellularly. Apart from these two features, insulin deficiency and insulin resistance have also been observed in AD brains. Thus, AD has also been referred to as type 3 diabetes by some of the scientists in this field. Insulin plays a pivotal role in learning and memory and is involved in regulating tau phosphorylation though the PI3KAkt-GSK3b signaling pathway. Interestingly, recent studies revealed that in AD brains the microglia transformed into a disease-associated microglia (DAM) status in a TREM2-dependent manner to restrain the toxicity of Aβ and propagation of tau. This also correlated with PI3K-Akt signaling through the adaptor of TREM2. Whether insulin has any effect on microglia activation in AD pathology is unclear so far. However, many studies demonstrated that diabetes increased the risk of AD. In this review, we summarize the main strategies for curing AD, including lowering the level of Aβ, suppressing the phosphorylation of tau, the ablation and/or repopulation of microglia, and especially the supply of insulin. We also propose that attention should be given to the influences of insulin on microglia in AD.
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spelling pubmed-97775262022-12-23 The Strategies for Treating “Alzheimer’s Disease”: Insulin Signaling May Be a Feasible Target You, Guanying Yao, Jinyi Liu, Qiong Li, Nan Curr Issues Mol Biol Review Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by senile plaques formed by amyloid-beta (Aβ) extracellularly and neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau protein intracellularly. Apart from these two features, insulin deficiency and insulin resistance have also been observed in AD brains. Thus, AD has also been referred to as type 3 diabetes by some of the scientists in this field. Insulin plays a pivotal role in learning and memory and is involved in regulating tau phosphorylation though the PI3KAkt-GSK3b signaling pathway. Interestingly, recent studies revealed that in AD brains the microglia transformed into a disease-associated microglia (DAM) status in a TREM2-dependent manner to restrain the toxicity of Aβ and propagation of tau. This also correlated with PI3K-Akt signaling through the adaptor of TREM2. Whether insulin has any effect on microglia activation in AD pathology is unclear so far. However, many studies demonstrated that diabetes increased the risk of AD. In this review, we summarize the main strategies for curing AD, including lowering the level of Aβ, suppressing the phosphorylation of tau, the ablation and/or repopulation of microglia, and especially the supply of insulin. We also propose that attention should be given to the influences of insulin on microglia in AD. MDPI 2022-12-07 /pmc/articles/PMC9777526/ /pubmed/36547082 http://dx.doi.org/10.3390/cimb44120421 Text en © 2022 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
You, Guanying
Yao, Jinyi
Liu, Qiong
Li, Nan
The Strategies for Treating “Alzheimer’s Disease”: Insulin Signaling May Be a Feasible Target
title The Strategies for Treating “Alzheimer’s Disease”: Insulin Signaling May Be a Feasible Target
title_full The Strategies for Treating “Alzheimer’s Disease”: Insulin Signaling May Be a Feasible Target
title_fullStr The Strategies for Treating “Alzheimer’s Disease”: Insulin Signaling May Be a Feasible Target
title_full_unstemmed The Strategies for Treating “Alzheimer’s Disease”: Insulin Signaling May Be a Feasible Target
title_short The Strategies for Treating “Alzheimer’s Disease”: Insulin Signaling May Be a Feasible Target
title_sort strategies for treating “alzheimer’s disease”: insulin signaling may be a feasible target
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777526/
https://www.ncbi.nlm.nih.gov/pubmed/36547082
http://dx.doi.org/10.3390/cimb44120421
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