Liraglutide prevents beta-amyloid-induced neurotoxicity in SH-SY5Y cells via a PI3K-dependent signaling pathway

Li, Xiaoying; Wang, Lin-Xi; Zhou, C.; Liu, Libin

doi:10.1080/01616412.2016.1145914

Cited by 33 publications

(13 citation statements)

References 16 publications

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“…In this study, combination of both drugs in both doses had significant effects on CK-MB and LDH. These findings were collaborated by Liu et al (2016) who stated that pre-treatment with liraglutide in human neuroblastoma cell line exposed to beta-amyloid Aβ decrease LDH leakage and cellular apoptosis. In the same direction, Sharma et al (2014) illustrated that liraglutide reduce LDH and apoptosis.…”

Section: Discussionsupporting

confidence: 49%

Impact of liraglutide versus atorvastatin on cardiovascular changes in rat model of adenine induced chronic renal failure

Shata¹,

Elmorsy²,

Elesawy³

et al. 2017

Afr. J. Pharm. Pharmacol.

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The prevalence of cardiovascular changes markedly increases with deterioration of patient's renal function and can stack up 65 to 70% in end-stage renal disease. A rapid fall in renal function is often associated with uncontrolled congestive heart failure. Beyond their lipid-lowering effect, statins have been shown to protect the heart in different diseases. Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue, used to control diabetes. It improves cardiac dysfunction in non-diabetics, but underlying mechanisms remain to some extent, unclear. Fifty two male Sprague-Dawley rats weighing 200 to 250 g were grouped into negative control, positive control, liraglutide treated group (0.3 mg/kg), atorvastatin treated group (10 mg/kg), liraglutide and atorvastatin treated group (0.3 and 10 mg/kg, respectively), liraglutide and atorvastatin treated group (0.15 and 5 mg/kg, respectively). Combination of both drugs significantly reduce creatine phosphokinase isoenzyme (CK-MB) in both doses (p<0.008, p <0.002) and lactate dehydrognase (LDH) (p<0.04, p<0.01). Liraglutide alone or in combination with atorvastatin in both doses (p<0.02, p<0.01 and p<0.01) significantly increased superoxide dismutase (SOD). Atorvastatin alone (p<0.02) or in combination with liraglutide in both doses (p<0.001, p<0.001) induced a significant decrease of malondialdehyde (MDA). Atorvastatin alone (p<0.01) or in combination with liraglutide in both doses induced a significant amelioration of nitric oxide (NO) and cholesterol (p<0.01 and p<0.02). Significant improvements in blood urea nitrogen (BUN) and glucose profile were seen with all tested drugs either single or in combination. Combined implementation of both drugs improves histopathological changes of cardiac muscle fibres. Liraglutide has promising effects on cardiovascular changes in adenine induced chronic nephropathy through modulation of LDH, CK-MB and improvement of NO and SOD. Also, it can mitigate fibrosis and cardiac tissue changes. Its effects markedly increase in conjunction with atorvastatin. Combined administration of liraglutide and atorvastatin in a high dose has a reliable effect on improving outcome in biochemical and histopthological cardiac muscle fibers changes.

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Section: Discussionsupporting

confidence: 49%

Impact of liraglutide versus atorvastatin on cardiovascular changes in rat model of adenine induced chronic renal failure

Shata¹,

Elmorsy²,

Elesawy³

et al. 2017

Afr. J. Pharm. Pharmacol.

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“…Furthermore, the PI3K-AKT pathway is associated with the activation and function of microglia, which are important resident cells of the central nervous system responsible for neuroinflammation (Zhong et al, 2017; Xu et al, 2018). More importantly, anti-diabetic drugs have been shown to prevent amyloid beta neurotoxicity in AD models through the activation of the PI3K-AKT pathway (Cai et al, 2014; Liu et al, 2016; Tumminia et al, 2018). Thus, targeting the PI3K-AKT pathway could be a potential therapeutic target for AD.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic and Network Analysis Highlight the Association of Diabetes at Different Stages of Alzheimer’s Disease

Santiago¹,

Bottero

Potashkin

2019

Front. Neurosci.

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Alzheimer’s disease (AD) and type 2 diabetes (T2D) are among the most prevalent chronic diseases affecting the aging population. Extensive research evidence indicates that T2D is a well-established risk factor for AD; however, the molecular mechanisms underlying this association have not been fully elucidated. Furthermore, how T2D may contribute to the progression of AD is a subject of extensive investigation. In this study, we compared the blood transcriptome of patients with mild cognitive impairment (MCI), AD, and advanced AD to those afflicted with T2D to unveil shared and unique pathways and potential therapeutic targets. Blood transcriptomic analyses revealed a positive correlation between gene expression profiles of MCI, AD, and T2D in seven independent microarrays. Interestingly, gene expression profiles from women with advanced AD correlated negatively with T2D, suggesting sex-specific differences in T2D as a risk factor for AD. Network and pathway analysis revealed that shared molecular networks between MCI and T2D were predominantly enriched in inflammation and infectious diseases whereas those networks shared between overt AD and T2D were involved in the phosphatidylinositol 3-kinase and protein kinase B/Akt (PI3K-AKT) signaling pathway, a major mediator of insulin signaling in the body. The PI3K-AKT signaling pathway became more significantly dysregulated in the advanced AD and T2D shared network. Furthermore, endocrine resistance and atherosclerosis pathways emerged as dysregulated pathways in the advanced AD and T2D shared network. Interestingly, network analysis of shared differentially expressed genes between children with T2D and MCI subjects identified forkhead box O3 (FOXO3) as a central transcriptional regulator, suggesting that it may be a potential therapeutic target for early intervention in AD. Collectively, these results suggest that T2D may be implicated at different stages of AD through different molecular pathways disrupted during the preclinical phase of AD and more advanced stages of the disease.

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“…In studies on AD mouse models, GLP-1 analogues reduced neuronal tau hyperphosphorylation, prevented synaptic loss, improved motor function, enhanced synaptic plasticity, attenuated memory and learning deficits and diminished beta amyloid plaque load in the brain [ 94 , 95 ]. The neuroprotective effects of liraglutide seem to be mediated through the PI3K-Akt signalling pathway [ 116 ] while those of lixisenatide were attributed to induced Akt and MEK signalling pathways [ 117 ].…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Type 2 Diabetes Mellitus and Alzheimer’s Disease: Role of Insulin Signalling and Therapeutic Implications

Tumminia

Vinciguerra

Parisi

et al. 2018

IJMS

190

127

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In the last two decades, numerous in vitro studies demonstrated that insulin receptors and theirs downstream pathways are widely distributed throughout the brain. This evidence has proven that; at variance with previous believes; insulin/insulin-like-growth-factor (IGF) signalling plays a crucial role in the regulation of different central nervous system (CNS) tasks. The most important of these functions include: synaptic formation; neuronal plasticity; learning; memory; neuronal stem cell activation; neurite growth and repair. Therefore; dysfunction at different levels of insulin signalling and metabolism can contribute to the development of a number of brain disorders. Growing evidences demonstrate a close relationship between Type 2 Diabetes Mellitus (T2DM) and neurodegenerative disorders such as Alzheimer’s disease. They, in fact, share many pathophysiological characteristics comprising impaired insulin sensitivity, amyloid β accumulation, tau hyper-phosphorylation, brain vasculopathy, inflammation and oxidative stress. In this article, we will review the clinical and experimental evidences linking insulin resistance, T2DM and neurodegeneration, with the objective to specifically focus on insulin signalling-related mechanisms. We will also evaluate the pharmacological strategies targeting T2DM as potential therapeutic tools in patients with cognitive impairment.

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Liraglutide prevents beta-amyloid-induced neurotoxicity in SH-SY5Y cells via a PI3K-dependent signaling pathway

Cited by 33 publications

References 16 publications

Impact of liraglutide versus atorvastatin on cardiovascular changes in rat model of adenine induced chronic renal failure

Impact of liraglutide versus atorvastatin on cardiovascular changes in rat model of adenine induced chronic renal failure

Transcriptomic and Network Analysis Highlight the Association of Diabetes at Different Stages of Alzheimer’s Disease

Type 2 Diabetes Mellitus and Alzheimer’s Disease: Role of Insulin Signalling and Therapeutic Implications

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