Investigating the role of P38, JNK and ERK in LPS induced hippocampal insulin resistance and spatial memory impairment: effects of insulin treatment

Iloun, Parisa; Abbasnejad, Zahra; Janahmadi, Mahyar; Ahmadiani, Abolhassan; Ghasemi, Rasoul

doi:10.17179/excli2018-1387

Cited by 5 publications

(1 citation statement)

References 49 publications

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“…Third, while insulin exerts anti-inflammatory effects, inflammation is also the primary cause of insulin resistance in the brain (see Figure 1 ; Holscher, 2019 ). For example, the i.c.v-injection of LPS caused memory impairments and desensitized insulin-signaling in the hippocampus of rats, as implied by Ser 307 -phosphorylated IRS-1 and decreased phospho-Akt levels, whereas insulin co-treatment rescued the latter ( Iloun et al, 2018 ). Mechanistically, similar to what happens in the periphery during T2DM, the TLR/NF-κB-mediated production and release of pro-inflammatory cytokines by stimulated microglia and astrocytes, including IL-1β, IL-6, IL-18, and TNF-α, result in PICR activation on neurons during AD and PD.…”

Section: Insulin Resistance and The Neuronal Energy Metabolismmentioning

confidence: 99%

The neuroprotective effects of glucagon-like peptide 1 in Alzheimer’s and Parkinson’s disease: An in-depth review

Reich

Hölscher

2022

Front. Neurosci.

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Currently, there is no disease-modifying treatment available for Alzheimer’s and Parkinson’s disease (AD and PD) and that includes the highly controversial approval of the Aβ-targeting antibody aducanumab for the treatment of AD. Hence, there is still an unmet need for a neuroprotective drug treatment in both AD and PD. Type 2 diabetes is a risk factor for both AD and PD. Glucagon-like peptide 1 (GLP-1) is a peptide hormone and growth factor that has shown neuroprotective effects in preclinical studies, and the success of GLP-1 mimetics in phase II clinical trials in AD and PD has raised new hope. GLP-1 mimetics are currently on the market as treatments for type 2 diabetes. GLP-1 analogs are safe, well tolerated, resistant to desensitization and well characterized in the clinic. Herein, we review the existing evidence and illustrate the neuroprotective pathways that are induced following GLP-1R activation in neurons, microglia and astrocytes. The latter include synaptic protection, improvements in cognition, learning and motor function, amyloid pathology-ameliorating properties (Aβ, Tau, and α-synuclein), the suppression of Ca2+ deregulation and ER stress, potent anti-inflammatory effects, the blockage of oxidative stress, mitochondrial dysfunction and apoptosis pathways, enhancements in the neuronal insulin sensitivity and energy metabolism, functional improvements in autophagy and mitophagy, elevated BDNF and glial cell line-derived neurotrophic factor (GDNF) synthesis as well as neurogenesis. The many beneficial features of GLP-1R and GLP-1/GIPR dual agonists encourage the development of novel drug treatments for AD and PD.

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Section: Insulin Resistance and The Neuronal Energy Metabolismmentioning

confidence: 99%

The neuroprotective effects of glucagon-like peptide 1 in Alzheimer’s and Parkinson’s disease: An in-depth review

Reich

Hölscher

2022

Front. Neurosci.

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Roles and Interaction of the MAPK Signaling Cascade in Aβ25–35-Induced Neurotoxicity Using an Isolated Primary Hippocampal Cell Culture System

et al. 2020

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Insulin Signaling Impairment in the Brain as a Risk Factor in Alzheimer’s Disease

Hölscher

2019

Front. Aging Neurosci.

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Type 2 diabetes is a risk factor for developing Alzheimer’s disease (AD). The underlying mechanism that links up the two conditions seems to be the de-sensitization of insulin signaling. In patients with AD, insulin signaling was found to be de-sensitized in the brain, even if they did not have diabetes. Insulin is an important growth factor that regulates cell growth, energy utilization, mitochondrial function and replacement, autophagy, oxidative stress management, synaptic plasticity, and cognitive function. Insulin desensitization, therefore, can enhance the risk of developing neurological disorders in later life. Other risk factors, such as high blood pressure or brain injury, also enhance the likelihood of developing AD. All these risk factors have one thing in common – they induce a chronic inflammation response in the brain. Pro-inflammatory cytokines block growth factor signaling and enhance oxidative stress. The underlying molecular processes for this are described in the review. Treatments to re-sensitize insulin signaling in the brain are also described, such as nasal insulin tests in AD patients, or treatments with re-sensitizing hormones, such as leptin, ghrelin, glucagon-like peptide 1 (GLP-1),and glucose-dependent insulinotropic polypeptide (GIP). The first clinical trials show promising results and are a proof of concept that utilizing such treatments is valid.

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Investigating the role of P38, JNK and ERK in LPS induced hippocampal insulin resistance and spatial memory impairment: effects of insulin treatment

Cited by 5 publications

References 49 publications

The neuroprotective effects of glucagon-like peptide 1 in Alzheimer’s and Parkinson’s disease: An in-depth review

The neuroprotective effects of glucagon-like peptide 1 in Alzheimer’s and Parkinson’s disease: An in-depth review

Roles and Interaction of the MAPK Signaling Cascade in Aβ25–35-Induced Neurotoxicity Using an Isolated Primary Hippocampal Cell Culture System

Insulin Signaling Impairment in the Brain as a Risk Factor in Alzheimer’s Disease

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