Exendin-4 Prevents Memory Loss and Neuronal Death in Rats with Sporadic Alzheimer-Like Disease

Zago, Adriana M.; Carvalho, Fabiano B.; Rahmeier, Francine L.; Santin, Marta; Guimarães, Giuliano R.; Gutierres, Jessié M.; da C. Fernandes, Marilda

doi:10.1007/s12035-023-03698-w

Cited by 7 publications

(3 citation statements)

References 72 publications

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“…Exendin-4 is a39–amino acid peptide agonist of GLP-1 [ 41 ] that increases insulin sensitivity in diabetes following cAMP/PKA signaling [ 42 ]. A recent study found that exendin-4 improved memory loss, synaptic plasticity, and neuronal death in hippocampal neurons in a streptozotocin-induced AD rat model [ 43 ]. Exenatide, a synthetic version of exendin-4, has been shown to improve cognitive performance and activate the expression of neurotrophic factors in a diabetic mouse model [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Positive Effects of Adiponectin, BDNF, and GLP-1 on Cortical Neurons Counteracting Palmitic Acid Induced Neurotoxicity

Jo,

Ahn,

Choi

et al. 2024

Clin Nutr Res

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The prevalence of metabolic syndrome caused by diets containing excessive fatty acids is increasing worldwide. Patients with metabolic syndrome exhibit abnormal lipid profiles, chronic inflammation, increased levels of saturated fatty acids, impaired insulin sensitivity, excessive fat accumulation, and neuropathological issues such as memory deficits. In particular, palmitic acid (PA) in saturated fatty acids aggravates inflammation, insulin resistance, impaired glucose tolerance, and synaptic failure. Recently, adiponectin, brain-derived neurotrophic factor (BDNF), and glucose-like peptide-1 (GLP-1) have been investigated to find therapeutic solutions for metabolic syndrome, with findings suggesting that they are involved in insulin sensitivity, enhanced lipid profiles, increased neuronal survival, and improved synaptic plasticity. We investigated the effects of adiponectin, BDNF, and GLP-1 on neurite outgrowth, length, and complexity in PA–treated primary cortical neurons using Sholl analysis. Our findings demonstrate the therapeutic potential of adiponectin, BDNF, and GLP-1 in enhancing synaptic plasticity within brains affected by metabolic imbalance. We underscore the need for additional research into the mechanisms by which adiponectin, BDNF, and GLP-1 influence neural complexity in brains with metabolic imbalances.

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Section: Discussionmentioning

confidence: 99%

Positive Effects of Adiponectin, BDNF, and GLP-1 on Cortical Neurons Counteracting Palmitic Acid Induced Neurotoxicity

Jo,

Ahn,

Choi

et al. 2024

Clin Nutr Res

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show abstract

“…Another study demonstrated the neuroprotective and neurotrophic effects of EXE-4 in the brain of mice that had undergone mild traumatic brain injury [108]. In 2023, Zago et al set out to investigate the effects of EX-4 on the memory and hippocampal neurons of rats with sporadic dementia of the Alzheimer's type (SDAT), in which the STZ-treated male Wistar rats were treated with EX-4 over a span of 21 days, during which memory and learning were assessed using a Y-maze (YM), object recognition tasks (ORTs), and object displacement tasks (ODTs) [109]. The results showed that the agonists of GLP-1R are anti-apoptotic, encourage the proliferation of hippocampal neurons, and preserve memory [109].…”

Section: Incretinsmentioning

confidence: 99%

“…In 2023, Zago et al set out to investigate the effects of EX-4 on the memory and hippocampal neurons of rats with sporadic dementia of the Alzheimer's type (SDAT), in which the STZ-treated male Wistar rats were treated with EX-4 over a span of 21 days, during which memory and learning were assessed using a Y-maze (YM), object recognition tasks (ORTs), and object displacement tasks (ODTs) [109]. The results showed that the agonists of GLP-1R are anti-apoptotic, encourage the proliferation of hippocampal neurons, and preserve memory [109]. Secondary outcomes from a small (n = 18) pilot clinical trial using Exenatide, the synthetic form of EX-4, revealed no benefit of exenatide; however, no firm conclusions can be drawn from this study due to its early termination [110].…”

Section: Incretinsmentioning

confidence: 99%

Pharmacological Approaches Using Diabetic Drugs Repurposed for Alzheimer’s Disease

Adem,

Decourt,

Sabbagh

2024

Biomedicines

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Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are chronic, progressive disorders affecting the elderly, which fosters global healthcare concern with the growing aging population. Both T2DM and AD have been linked with increasing age, advanced glycosylation end products, obesity, and insulin resistance. Insulin resistance in the periphery is significant in the development of T2DM and it has been posited that insulin resistance in the brain plays a key role in AD pathogenesis, earning AD the name “type 3 diabetes”. These clinical and epidemiological links between AD and T2DM have become increasingly pronounced throughout the years, and serve as a means to investigate the effects of antidiabetic therapies in AD, such as metformin, intranasal insulin, incretins, DPP4 inhibitors, PPAR-γ agonists, SGLT2 inhibitors. The majority of these drugs have shown benefit in preclinical trials, and have shown some promising results in clinical trials, with the improvement of cognitive faculties in participants with mild cognitive impairment and AD. In this review, we have summarize the benefits, risks, and conflicting data that currently exist for diabetic drugs being repurposed for the treatment of AD.

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Curcumin triggers the Wnt/β-catenin pathway and shields neurons from injury caused by intermittent hypoxia

He,

Zhao,

et al. 2024

Tissue and Cell

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Exendin-4 Prevents Memory Loss and Neuronal Death in Rats with Sporadic Alzheimer-Like Disease

Cited by 7 publications

References 72 publications

Positive Effects of Adiponectin, BDNF, and GLP-1 on Cortical Neurons Counteracting Palmitic Acid Induced Neurotoxicity

Positive Effects of Adiponectin, BDNF, and GLP-1 on Cortical Neurons Counteracting Palmitic Acid Induced Neurotoxicity

Pharmacological Approaches Using Diabetic Drugs Repurposed for Alzheimer’s Disease

Curcumin triggers the Wnt/β-catenin pathway and shields neurons from injury caused by intermittent hypoxia

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