Cargando…
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...
Autores principales: | , , , |
---|---|
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 |
_version_ | 1784856126548869120 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9777526 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT youguanying thestrategiesfortreatingalzheimersdiseaseinsulinsignalingmaybeafeasibletarget AT yaojinyi thestrategiesfortreatingalzheimersdiseaseinsulinsignalingmaybeafeasibletarget AT liuqiong thestrategiesfortreatingalzheimersdiseaseinsulinsignalingmaybeafeasibletarget AT linan thestrategiesfortreatingalzheimersdiseaseinsulinsignalingmaybeafeasibletarget AT youguanying strategiesfortreatingalzheimersdiseaseinsulinsignalingmaybeafeasibletarget AT yaojinyi strategiesfortreatingalzheimersdiseaseinsulinsignalingmaybeafeasibletarget AT liuqiong strategiesfortreatingalzheimersdiseaseinsulinsignalingmaybeafeasibletarget AT linan strategiesfortreatingalzheimersdiseaseinsulinsignalingmaybeafeasibletarget |