DPP-4 inhibitor improves learning and memory deficits and AD-like neurodegeneration by modulating the GLP-1 signaling

Chen, Shuyi; Zhou, Mei; Sun, Jie; Guo, Aihuan; Fernando, Roger Lakmal; Chen, Yanlin; Peng, Peng; Zhao, Gang; Deng, Yanqiu

doi:10.1016/j.neuropharm.2019.107668

Cited by 56 publications

(41 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, another study suggested that exenatide could enhance BDNF signaling and reduce inflammation in AD mouse model, but it failed to promote changes in cognitive function( Bomba et al, 2019 ). DPP-4 inhibitors, sitagliptin and saxagliptin, also protected learning and memory function in AD mouse model through increasing the O-Glycosylation and decreasing abnormal phosphorylation of tau and neurofilaments (NFs), reducing intercellular Aβ accumulation and alleviating neurodegeneration related to GLP-1 signaling pathway( Chen et al, 2019b ). Additionally, saxagliptin and vildagliptin reduced inflammation in streptozotocin-induced AD mice( Kosaraju et al, 2013a ; Kosaraju et al, 2013b ).…”

Section: Repurposing Of Anti-diabetic Agents As a Potential Treatment Targeting Cognitive Function In Ad And Schizophreniamentioning

confidence: 99%

Repurposing of Anti-Diabetic Agents as a New Opportunity to Alleviate Cognitive Impairment in Neurodegenerative and Neuropsychiatric Disorders

Chen

Cao

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Cognitive impairment is a shared abnormality between type 2 diabetes mellitus (T2DM) and many neurodegenerative and neuropsychiatric disorders, such as Alzheimer’s disease (AD) and schizophrenia. Emerging evidence suggests that brain insulin resistance plays a significant role in cognitive deficits, which provides the possibility of anti-diabetic agents repositioning to alleviate cognitive deficits. Both preclinical and clinical studies have evaluated the potential cognitive enhancement effects of anti-diabetic agents targeting the insulin pathway. Repurposing of anti-diabetic agents is considered to be promising for cognitive deficits prevention or control in these neurodegenerative and neuropsychiatric disorders. This article reviewed the possible relationship between brain insulin resistance and cognitive deficits. In addition, promising therapeutic interventions, especially current advances in anti-diabetic agents targeting the insulin pathway to alleviate cognitive impairment in AD and schizophrenia were also summarized.

show abstract

Section: Repurposing Of Anti-diabetic Agents As a Potential Treatment Targeting Cognitive Function In Ad And Schizophreniamentioning

confidence: 99%

Repurposing of Anti-Diabetic Agents as a New Opportunity to Alleviate Cognitive Impairment in Neurodegenerative and Neuropsychiatric Disorders

Chen

Cao

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Inhibitors of DPP-4 also increase GLP-1 signaling activation by inhibiting the degradation of GLP-1 [ 162 ]. Therefore, they potentially act on AD, like other GLP-1 analogs [ 163 ]. They also lead to increased adiponectin and are thought to be alternative medications for AD [ 164 , 165 , 166 , 167 ].…”

Section: Adiponectin-associated Therapeutic Strategy Against Ad Inmentioning

confidence: 99%

Adiponectin: The Potential Regulator and Therapeutic Target of Obesity and Alzheimer’s Disease

Kim

Barua

Jeong

et al. 2020

IJMS

View full text Add to dashboard Cite

Animal and human mechanistic studies have consistently shown an association between obesity and Alzheimer’s disease (AD). AD, a degenerative brain disease, is the most common cause of dementia and is characterized by the presence of extracellular amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles disposition. Some studies have recently demonstrated that Aβ and tau cannot fully explain the pathophysiological development of AD and that metabolic disease factors, such as insulin, adiponectin, and antioxidants, are important for the sporadic onset of nongenetic AD. Obesity prevention and treatment can be an efficacious and safe approach to AD prevention. Adiponectin is a benign adipokine that sensitizes the insulin receptor signaling pathway and suppresses inflammation. It has been shown to be inversely correlated with adipose tissue dysfunction and may enhance the risk of AD because a range of neuroprotection adiponectin mechanisms is related to AD pathology alleviation. In this study, we summarize the recent progress that addresses the beneficial effects and potential mechanisms of adiponectin in AD. Furthermore, we review recent studies on the diverse medications of adiponectin that could possibly be related to AD treatment, with a focus on their association with adiponectin. A better understanding of the neuroprotection roles of adiponectin will help clarify the precise underlying mechanism of AD development and progression.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that the activation of GLP-1R could improve impaired learning and memory function [6,[24][25][26]. It was detected that GLP-1 and GLP-1R were both decreased in AD human brain and APP/PS1/Tau transgenic (3xTg) murine brains [26]. However, improving the level of GLP-1and GLP-1R expression by dipeptidyl peptidase-4 (DPP-4) inhibitors in the hippocampus and cortex of AD mice brains could improve impaired learning and memory, increase the O-Glycosylation and synaptic proteins, and decrease abnormal phosphorylation of tau and neuro laments (NFs) and intercellular β-amyloid (Aβ) accumulation [26].…”

Section: Discussionmentioning

confidence: 99%

GLP-1R Activation Ameliorate Novel-object Recognition Function via Hippocampal AMPK/NF-κB Signaling Pathway in Neuropathic Pain Mice

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Growing evidences indicate that neuropathic pain is frequently accompanied with cognitive impairments, which aggravate the decrease in the quality of life of chronic pain patients. Furthermore, it has been shown that the activation of Glucagon-like-peptide-1receptor (GLP-1R) improved memory deficit in multiple diseases such as Alzheimer’s disease (AD), stroke and so on. However, whether activating GLP-1R could improve memory impairment induced by neuropathic pain and the mechanism by which this improvement would occur remain unclear. Methods: The spared nerve injury (SNI) model was established as a kind of neuropathic pain. And novel-object recognition memory (hippocampus-dependent memory) was tested by the novel object recognition test (NORT).The expression levels of GLP-1,GLP-1R,adenosine monophosphate-activated protein kinase (AMPK),p-AMPKThr172, nuclear factor κ B p65 (NF-κB p65), interleukin-1β p17(IL-1β p17),and the synaptic associated proteins were tested in the murine hippocampus with memory deficits caused by neuropathic pain. Then, exenatide acetate (Ex-4, a GLP-1R agonist), exendin(9-39)(Ex(9-39),a GLP-1R antagonist) and Compound C dihydrochloride ( CC, an AMPK inhibitor) were used to test the effects of activating GLP-1R in mice with neuropathic pain.Results: First, we uncovered that neuropathic pain could inhibit GLP-1/GLP-R axis, disturb inflammatory signaling pathway, increase the expression of IL-1β and downregulate the synaptic associated proteins (postsynaptic density protein 95(PSD95) and Arc). Subsequently, we reported that Ex-4 treatment could improve recognition memory impairment and increase the ratio of p-AMPKThr172/AMPK, decrease the expression of NF-κB p65 and IL-1β p17, upregulate the levels of PSD95 and Arc. Moreover, we uncovered that Ex(9-39) and CC treatment could abrogate the neuroprotection of Ex-4 in mice with memory impairment induced by neuropathic pain.Conclusions: The results indicated that the activation of GLP-1R could improve recognition memory impairment caused by neuropathic pain via activating AMPK signaling pathway, then, which could inhibit NF-κB activating and its downstream IL-1β expression, upregulate the levels of PSD95 and Arc proteins.

show abstract

DPP-4 inhibitor improves learning and memory deficits and AD-like neurodegeneration by modulating the GLP-1 signaling

Cited by 56 publications

References 81 publications

Repurposing of Anti-Diabetic Agents as a New Opportunity to Alleviate Cognitive Impairment in Neurodegenerative and Neuropsychiatric Disorders

Repurposing of Anti-Diabetic Agents as a New Opportunity to Alleviate Cognitive Impairment in Neurodegenerative and Neuropsychiatric Disorders

Adiponectin: The Potential Regulator and Therapeutic Target of Obesity and Alzheimer’s Disease

GLP-1R Activation Ameliorate Novel-object Recognition Function via Hippocampal AMPK/NF-κB Signaling Pathway in Neuropathic Pain Mice

Contact Info

Product

Resources

About