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Neuroprotection by dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide-1 analogs via the modulation of AKT-signaling pathway in Alzheimer’s disease

Alzheimer’s disease (AD) is the most common reason for progressive dementia in the elderly. It has been shown that disorders of the mammalian/mechanistic target of rapamycin (mTOR) signaling pathways are related to the AD. On the other hand, diabetes mellitus (DM) is a risk factor for the cognitive...

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Autores principales: Ikeda, Yuka, Nagase, Nozomi, Tsuji, Ai, Kitagishi, Yasuko, Matsuda, Satoru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637616/
https://www.ncbi.nlm.nih.gov/pubmed/34904048
http://dx.doi.org/10.4331/wjbc.v12.i6.104
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author Ikeda, Yuka
Nagase, Nozomi
Tsuji, Ai
Kitagishi, Yasuko
Matsuda, Satoru
author_facet Ikeda, Yuka
Nagase, Nozomi
Tsuji, Ai
Kitagishi, Yasuko
Matsuda, Satoru
author_sort Ikeda, Yuka
collection PubMed
description Alzheimer’s disease (AD) is the most common reason for progressive dementia in the elderly. It has been shown that disorders of the mammalian/mechanistic target of rapamycin (mTOR) signaling pathways are related to the AD. On the other hand, diabetes mellitus (DM) is a risk factor for the cognitive dysfunction. The pathogenesis of the neuronal impairment caused by diabetic hyperglycemia is intricate, which contains neuro-inflammation and/or neurodegeneration and dementia. Glucagon-like peptide-1 (GLP1) is interesting as a possible link between metabolism and brain impairment. Modulation of GLP1 activity can influence amyloid-beta peptide aggregation via the phosphoinositide-3 kinase/AKT/mTOR signaling pathway in AD. The GLP1 receptor agonists have been shown to have favorable actions on the brain such as the improvement of neurological deficit. They might also exert a beneficial effect with refining learning and memory on the cognitive impairment induced by diabetes. Recent experimental and clinical evidence indicates that dipeptidyl-peptidase-4 (DPP4) inhibitors, being currently used for DM therapy, may also be effective for AD treatment. The DPP-4 inhibitors have demonstrated neuroprotection and cognitive improvements in animal models. Although further studies for mTOR, GLP1, and DPP4 signaling pathways in humans would be intensively required, they seem to be a promising approach for innovative AD-treatments. We would like to review the characteristics of AD pathogenesis, the key roles of mTOR in AD and the preventive and/ or therapeutic suggestions of directing the mTOR signaling pathway.
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spelling pubmed-86376162021-12-12 Neuroprotection by dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide-1 analogs via the modulation of AKT-signaling pathway in Alzheimer’s disease Ikeda, Yuka Nagase, Nozomi Tsuji, Ai Kitagishi, Yasuko Matsuda, Satoru World J Biol Chem Minireviews Alzheimer’s disease (AD) is the most common reason for progressive dementia in the elderly. It has been shown that disorders of the mammalian/mechanistic target of rapamycin (mTOR) signaling pathways are related to the AD. On the other hand, diabetes mellitus (DM) is a risk factor for the cognitive dysfunction. The pathogenesis of the neuronal impairment caused by diabetic hyperglycemia is intricate, which contains neuro-inflammation and/or neurodegeneration and dementia. Glucagon-like peptide-1 (GLP1) is interesting as a possible link between metabolism and brain impairment. Modulation of GLP1 activity can influence amyloid-beta peptide aggregation via the phosphoinositide-3 kinase/AKT/mTOR signaling pathway in AD. The GLP1 receptor agonists have been shown to have favorable actions on the brain such as the improvement of neurological deficit. They might also exert a beneficial effect with refining learning and memory on the cognitive impairment induced by diabetes. Recent experimental and clinical evidence indicates that dipeptidyl-peptidase-4 (DPP4) inhibitors, being currently used for DM therapy, may also be effective for AD treatment. The DPP-4 inhibitors have demonstrated neuroprotection and cognitive improvements in animal models. Although further studies for mTOR, GLP1, and DPP4 signaling pathways in humans would be intensively required, they seem to be a promising approach for innovative AD-treatments. We would like to review the characteristics of AD pathogenesis, the key roles of mTOR in AD and the preventive and/ or therapeutic suggestions of directing the mTOR signaling pathway. Baishideng Publishing Group Inc 2021-11-27 2021-11-27 /pmc/articles/PMC8637616/ /pubmed/34904048 http://dx.doi.org/10.4331/wjbc.v12.i6.104 Text en ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved. https://creativecommons.org/licenses/by-nc/4.0/This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
spellingShingle Minireviews
Ikeda, Yuka
Nagase, Nozomi
Tsuji, Ai
Kitagishi, Yasuko
Matsuda, Satoru
Neuroprotection by dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide-1 analogs via the modulation of AKT-signaling pathway in Alzheimer’s disease
title Neuroprotection by dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide-1 analogs via the modulation of AKT-signaling pathway in Alzheimer’s disease
title_full Neuroprotection by dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide-1 analogs via the modulation of AKT-signaling pathway in Alzheimer’s disease
title_fullStr Neuroprotection by dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide-1 analogs via the modulation of AKT-signaling pathway in Alzheimer’s disease
title_full_unstemmed Neuroprotection by dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide-1 analogs via the modulation of AKT-signaling pathway in Alzheimer’s disease
title_short Neuroprotection by dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide-1 analogs via the modulation of AKT-signaling pathway in Alzheimer’s disease
title_sort neuroprotection by dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide-1 analogs via the modulation of akt-signaling pathway in alzheimer’s disease
topic Minireviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637616/
https://www.ncbi.nlm.nih.gov/pubmed/34904048
http://dx.doi.org/10.4331/wjbc.v12.i6.104
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