Ikeda Y, Nagase N, Tsuji A, Kitagishi Y, Matsuda S. Neuroprotection by dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide-1 analogs via the modulation of AKT-signaling pathway in Alzheimer’s disease. World J Biol Chem 2021; 12(6): 104-113 [PMID: 34904048 DOI: 10.4331/wjbc.v12.i6.104]
Corresponding Author of This Article
Satoru Matsuda, MD, PhD, Professor, Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan. smatsuda@cc.nara-wu.ac.jp
Research Domain of This Article
Neurosciences
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Biol Chem. Nov 27, 2021; 12(6): 104-113 Published online Nov 27, 2021. doi: 10.4331/wjbc.v12.i6.104
Neuroprotection by dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide-1 analogs via the modulation of AKT-signaling pathway in Alzheimer’s disease
Yuka Ikeda, Nozomi Nagase, Ai Tsuji, Yasuko Kitagishi, Satoru Matsuda
Yuka Ikeda, Nozomi Nagase, Ai Tsuji, Yasuko Kitagishi, Satoru Matsuda, Food Science and Nutrition, Nara Women’s University, Nara 630-8506, Japan
Author contributions: Each author (Ikeda Y, Nagase N, Tsuji A, Kitagishi Y, Matsuda S) participated sufficiently in this work of drafting the article and/or revising the article for the important rational content; all authors gave final approval of the version to be submitted.
Conflict-of-interest statement: The authors declare that they have no competing financial interests.
Open-Access: 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/
Corresponding author: Satoru Matsuda, MD, PhD, Professor, Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan. smatsuda@cc.nara-wu.ac.jp
Received: March 26, 2021 Peer-review started: March 26, 2021 First decision: May 6, 2021 Revised: May 21, 2021 Accepted: November 28, 2021 Article in press: November 28, 2021 Published online: November 27, 2021 Processing time: 263 Days and 2.8 Hours
Abstract
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.
Core Tip: Disorders of mammalian/mechanistic target of rapamycin (mTOR) signaling pathways are related to Alzheimer’s disease (AD). Although further studies for mTOR, glucagon-like peptide-1, and dipeptidyl-peptidase-4 signaling are needed, they seem to be a promising approach for innovative AD-treatments.
