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Liraglutide alzheimers

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https://www.readbyqxmd.com/read/29705602/liraglutide-attenuates-the-depressive-and-anxiety-like-behaviour-in-the-corticosterone-induced-depression-model-via-improving-hippocampal-neural-plasticity
#1
Han Weina, Niu Yuhu, Holscher Christian, Li Birong, Shen Feiyu, Wang Le
Recent studies indicate that metabolic disorders such as diabetes and obesity are a major risk factor of psychiatric diseases. This relationship opens the opportunity to develop new antidepressant drugs by repurposing antidiabetic drugs. Previous research has demonstrated that GLP-1 analogs are neuroprotective in several neurological disease models including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In addition, the GLP-1 analog liraglutide has been shown to promote neurogenesis, which is seen to play important roles in memory formation and cognitive and emotional processing...
April 26, 2018: Brain Research
https://www.readbyqxmd.com/read/29614684/novel-lipidized-analog-of-prolactin-releasing-peptide-improves-memory-impairment-and-attenuates-hyperphosphorylation-of-tau-protein-in-a-mouse-model-of-tauopathy
#2
Andrea Popelová, Veronika Pražienková, Barbora Neprašová, Barbora Judita Kasperová, Lucie Hrubá, Martina Holubová, Jana Zemenová, David Blum, Blanka Železná, Marie-Christine Galas, Jaroslav Kuneš, Lenka Maletínská
Obesity and type 2 diabetes mellitus (T2DM) were characterized as risk factors for Alzheimer's disease (AD) development. Subsequently, T2DM drugs, such as liraglutide, were proven to be neuroprotective compounds attenuating levels of amyloid deposits, and tau hyperphosphorylation, both hallmarks of AD. The central anorexigenic effects of liraglutide inspired us to examine the potential neuroprotective effects of palm11-PrRP31, a strong anorexigenic analog with glucose-lowering properties, in THY-Tau22 mice overexpressing mutated human tau, a model of AD-like tau pathology...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29549796/post-treatment-with-the-glp-1-analogue-liraglutide-alleviate-chronic-inflammation-and-mitochondrial-stress-induced-by-status-epilepticus
#3
Rui-Fang Wang, Guo-Fang Xue, Christian Hölscher, Miao-Jing Tian, Peng Feng, Ji-Ying Zheng, Dong-Fang Li
Glucagon-like peptide-1(GLP-1) is a growth factor that has neuroprotective and anti-inflammatory properties. The protease resistant GLP-1 analogue liraglutide has been shown to be neuroprotective in previous studies in animal models of Alzheimer's disease or Parkinson's disease. Status epilepticus (SE) is a complex disorder, involving many underlying pathological processes, including excitotoxic and chronic inflammatory events. The present pilot study aims to investigate whether liraglutide alleviates the chronic inflammation response and mitochondrial stress induced by SE in the lithium-pilocarpine animal model...
March 9, 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29435980/the-diabetes-drug-liraglutide-reverses-cognitive-impairment-in-mice-and-attenuates-insulin-receptor-and-synaptic-pathology-in-a-non-human-primate-model-of-alzheimer-s-disease
#4
Andre F Batista, Leticia Forny-Germano, Julia R Clarke, Natalia M Lyra E Silva, Jordano Brito-Moreira, Susan E Boehnke, Andrew Winterborn, Brian C Coe, Ann Lablans, Juliana F Vital, Suelen A Marques, Ana Mb Martinez, Matthias Gralle, Christian Holscher, William L Klein, Jean-Christophe Houzel, Sergio T Ferreira, Douglas P Munoz, Fernanda G De Felice
Alzheimer's disease (AD) is a devastating neurological disorder that still lacks an effective treatment, and this has stimulated an intense pursuit of disease-modifying therapeutics. Given the increasingly recognized link between AD and defective brain insulin signaling, we investigated the actions of liraglutide, a glucagon-like peptide-1 (GLP-1) analog marketed for treatment of type 2 diabetes, in experimental models of AD. Insulin receptor pathology is an important feature of AD brains that impairs the neuroprotective actions of central insulin signaling...
May 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29235507/blood-brain-glucose-transfer-in-alzheimer-s-disease-effect-of-glp-1-analog-treatment
#5
Michael Gejl, Birgitte Brock, Lærke Egefjord, Kim Vang, Jørgen Rungby, Albert Gjedde
There are fewer than normal glucose transporters at the blood-brain barrier (BBB) in Alzheimer's disease (AD). When reduced expression of transporters aggravates the symptoms of AD, the transporters become a potential target of therapy. The incretin hormone GLP-1 prevents the decline of cerebral metabolic rate for glucose (CMRglc ) in AD, and GLP-1 may serve to raise transporter numbers. We hypothesized that the GLP-1 analog liraglutide would prevent the decline of CMRglc in AD by raising blood-brain glucose transfer, depending on the duration of disease...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29170452/liraglutide-restores-chronic-er-stress-autophagy-impairments-and-apoptotic-signalling-in-sh-sy5y-cells
#6
Theodora Panagaki, Maria Michael, Christian Hölscher
Growing evidence suggests that agonists of glucagon-like peptide (GLP-1) receptor exert neuroprotective and neurorestorative effects across a range of experimental models of neuronal degeneration, and, recently, a pilot clinical trial of Liraglutide in Alzheimer's disease patients showed improvements in cerebral glucose consumption that signifies disease progression. However, the exact underlying mechanism of action remains unclear. Chronic endoplasmic reticulum (ER) stress has recently emerged as a mechanism for neuronal injury, rendering it a potent therapeutic target for acute and chronic neurodegenerative disorders...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28382596/liraglutide-improves-water-maze-learning-and-memory-performance-while-reduces-hyperphosphorylation-of-tau-and-neurofilaments-in-app-ps1-tau-triple-transgenic-mice
#7
Shuyi Chen, Jie Sun, Gang Zhao, Ai Guo, Yanlin Chen, Rongxia Fu, Yanqiu Deng
The purpose of this study was to explore how liraglutide affects AD-like pathology and cognitive function in APP/PS1/Tau triple transgenic (3 × Tg) Alzheimer disease (AD) model mice. Male 3 × Tg mice and C57BL/6 J mice were treated for 8 weeks with liraglutide (300 μg/kg/day, subcutaneous injection) or saline. Levels of phosphorylated tau, neurofilaments (NFs), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) in brain tissues were assessed with western blots. Fluoro-Jade-B labeling were applied to detect pathological changes...
August 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28337257/subcutaneous-liraglutide-ameliorates-methylglyoxal-induced-alzheimer-like-tau-pathology-and-cognitive-impairment-by-modulating-tau-hyperphosphorylation-and-glycogen-synthase-kinase-3%C3%AE
#8
Liqin Qi, Zhou Chen, Yanping Wang, Xiaoying Liu, Xiaohong Liu, Linfang Ke, Zhongjie Zheng, Xiaowei Lin, Yu Zhou, Lijuan Wu, Libin Liu
Memory deterioration and synapse damage with accumulation of β-amyloid and hyperphosphorylated tau are hallmark lesions of Alzheimer's disease (AD). Methylglyoxal (MG), a key intermediate of glucose metabolism, is elevated in AD brains and modifies Aβ42, increasing misfolding and leading to the accumulation of senile plaques. Liraglutide, an analog of glucagon-like peptide-1 (GLP-1), is neurotrophic and neuroprotective. However, whether liraglutide can protect against AD-like memory-related deficits and tau hyperphosphorylation caused by MG in vivo is not known...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/27766537/a-novel-bioresorbable-device-as-a-controlled-release-system-for-protecting-cells-from-oxidative-stress-from-alzheimer-s-disease
#9
Geisa Nogueira Salles, Fernanda Aparecida Dos Santos Pereira, Cristina Pacheco-Soares, Fernanda Roberta Marciano, Christian Hölscher, Thomas J Webster, Anderson Oliveira Lobo
Bioresorbable electrospun fibres have highly functional features that can preserve drug efficacy, avoiding premature degradation, and control drug release rates over long periods. In parallel, it is known that Alzheimer's disease (AD) has been linked to impaired insulin signalling in the brain. Glucagon-like peptide 1 (GLP-1) analogues have beneficial effects on insulin release and possess exceptional neuroprotective properties. Herein, we describe for the first time the incorporation of a GLP-1 analogue, liraglutide, into electrospun poly (lactic acid) (PLA) fibres with in situ gelatin capsules, in order to provide the controlled release of liraglutide, improving neuroprotective properties...
November 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/27421117/long-term-treatment-with-liraglutide-a-glucagon-like-peptide-1-glp-1-receptor-agonist-has-no-effect-on-%C3%AE-amyloid-plaque-load-in-two-transgenic-app-ps1-mouse-models-of-alzheimer-s-disease
#10
Henrik H Hansen, Katrine Fabricius, Pernille Barkholt, Pernille Kongsbak-Wismann, Chantal Schlumberger, Jacob Jelsing, Dick Terwel, Annelies Termont, Charles Pyke, Lotte Bjerre Knudsen, Niels Vrang
One of the major histopathological hallmarks of Alzheimer's disease (AD) is cerebral deposits of extracellular β-amyloid peptides. Preclinical studies have pointed to glucagon-like peptide 1 (GLP-1) receptors as a potential novel target in the treatment of AD. GLP-1 receptor agonists, including exendin-4 and liraglutide, have been shown to promote plaque-lowering and mnemonic effects of in a number of experimental models of AD. Transgenic mouse models carrying genetic mutations of amyloid protein precursor (APP) and presenilin-1 (PS1) are commonly used to assess the pharmacodynamics of potential amyloidosis-lowering and pro-cognitive compounds...
2016: PloS One
https://www.readbyqxmd.com/read/27276528/incretin-based-therapy-for-type-2-diabetes-mellitus-is-promising-for-treating-neurodegenerative-diseases
#11
REVIEW
Yanwei Li, Lin Li, Christian Hölscher
Incretin hormones include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Due to their promising action on insulinotropic secretion and improving insulin resistance (IR), incretin-based therapies have become a new class of antidiabetic agents for the treatment of type 2 diabetes mellitus (T2DM). Recently, the links between neurodegenerative diseases and T2DM have been identified in a number of studies, which suggested that shared mechanisms, such as insulin dysregulation or IR, may underlie these conditions...
October 1, 2016: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/27252647/in-alzheimer-s-disease-6-month-treatment-with-glp-1-analog-prevents-decline-of-brain-glucose-metabolism-randomized-placebo-controlled-double-blind-clinical-trial
#12
Michael Gejl, Albert Gjedde, Lærke Egefjord, Arne Møller, Søren B Hansen, Kim Vang, Anders Rodell, Hans Brændgaard, Hanne Gottrup, Anna Schacht, Niels Møller, Birgitte Brock, Jørgen Rungby
In animal models, the incretin hormone GLP-1 affects Alzheimer's disease (AD). We hypothesized that treatment with GLP-1 or an analog of GLP-1 would prevent accumulation of Aβ and raise, or prevent decline of, glucose metabolism (CMRglc) in AD. In this 26-week trial, we randomized 38 patients with AD to treatment with the GLP-1 analog liraglutide (n = 18), or placebo (n = 20). We measured Aβ load in brain with tracer [(11)C]PIB (PIB), CMRglc with [(18)F]FDG (FDG), and cognition with the WMS-IV scale (ClinicalTrials...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27199640/one-for-all-hitting-multiple-alzheimer-s-disease-targets-with-one-drug
#13
REVIEW
Rebecca E Hughes, Katarina Nikolic, Rona R Ramsay
HIGHLIGHTS Many AD target combinations are being explored for multi-target drug design.New databases and models increase the potential of computational drug designLiraglutide and other antidiabetics are strong candidates for repurposing to AD.Donecopride a dual 5-HT/AChE inhibitor shows promise in pre-clinical studies Alzheimer's Disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27131827/subcutaneous-administration-of-liraglutide-ameliorates-learning-and-memory-impairment-by-modulating-tau-hyperphosphorylation-via-the-glycogen-synthase-kinase-3%C3%AE-pathway-in-an-amyloid-%C3%AE-protein-induced-alzheimer-disease-mouse-model
#14
Liqin Qi, Linfang Ke, Xiaohong Liu, Lianming Liao, Sujie Ke, Xiaoying Liu, Yanping Wang, Xiaowei Lin, Yu Zhou, Lijuan Wu, Zhou Chen, Libin Liu
Type 2 diabetes mellitus is a risk factor for Alzheimer's disease (AD). The glucagon-like peptide-1 analog liraglutide, a novel long-lasting incretin hormone, has been used to treat type 2 diabetes mellitus. In addition, liraglutide has been shown to be neurotrophic and neuroprotective. Here, we investigated the effects of liraglutide on amyloid β protein (Aβ)-induced AD in mice and explored its mechanism of action. The results showed that subcutaneous administration of liraglutide (25nmol/day), once daily for 8 weeks, prevented memory impairments in the Y Maze and Morris Water Maze following Aβ1-42 intracerebroventricular injection, and alleviated the ultra-structural changes of pyramidal neurons and chemical synapses in the hippocampal CA1 region...
July 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27108910/liraglutide-prevents-beta-amyloid-induced-neurotoxicity-in-sh-sy5y-cells-via-a-pi3k-dependent-signaling-pathway
#15
Xiao-Ying Liu, Lin-Xi Wang, Zhou Chen, Li-Bin Liu
OBJECTIVES: The aim of the study was to investigate the effects of the GLP-1 analog liraglutide on beta-amyloid (Aβ)-induced neurotoxicity in the human neuroblastoma cell line SH-SY5Y and study the underlying mechanisms. METHODS: Cultured SH-SY5Y cells in vitro were randomly divided into normal control group, beta-amyloid (Aβ) group (20, 40, and 80 uM), and liraglutide pre-treatment group (10, 100, and 200 nM). Cell viability was determined by CCK-8 and lactate dehydrogenase (LDH)...
April 2016: Neurological Research
https://www.readbyqxmd.com/read/26746341/the-glp-1-receptor-agonist-liraglutide-reduces-pathology-specific-tau-phosphorylation-and-improves-motor-function-in-a-transgenic-htaup301l-mouse-model-of-tauopathy
#16
Henrik H Hansen, Pernille Barkholt, Katrine Fabricius, Jacob Jelsing, Dick Terwel, Charles Pyke, Lotte Bjerre Knudsen, Niels Vrang
In addition to a prominent role in glycemic control, glucagon-like peptide 1 (GLP-1) receptor agonists exhibit neuroprotective properties. There is mounting experimental evidence that GLP-1 receptor agonists, including liraglutide, may enhance synaptic plasticity, counteract cognitive deficits and ameliorate neurodegenerative features in preclinical models of Alzheimer's disease (AD), predominantly in the context of β-amyloid toxicity. Here we characterized the effects of liraglutide in a transgenic mutant tau (hTauP301L) mouse tauopathy model, which develops age-dependent pathology-specific neuronal tau phosphorylation and neurofibrillary tangle formation with progressively compromised motor function (limb clasping)...
March 1, 2016: Brain Research
https://www.readbyqxmd.com/read/26205827/prophylactic-liraglutide-treatment-prevents-amyloid-plaque-deposition-chronic-inflammation-and-memory-impairment-in-app-ps1-mice
#17
Paula L McClean, Jaishree Jalewa, Christian Hölscher
Type 2 diabetes is a risk factor for Alzheimer's disease (AD). Previously, we have shown that the diabetes drug liraglutide is protective in middle aged and in old APP/PS1 mice. Here, we show that liraglutide has prophylactic properties. When injecting liraglutide once-daily ip. in two months old mice for 8 months, the main hallmarks of AD were much reduced. Memory formation in object recognition and Morris water maze were normalised and synapse loss and the loss of synaptic plasticity was prevented. In addition, amyloid plaque load, including dense core congophilic plaques, was much reduced...
October 15, 2015: Behavioural Brain Research
https://www.readbyqxmd.com/read/26183127/early-intervention-with-glucagon-like-peptide-1-analog-liraglutide-prevents-tau-hyperphosphorylation-in-diabetic-db-db-mice
#18
De-Lin Ma, Fu-Qiong Chen, Wei-Jie Xu, Wen-Zhu Yue, Gang Yuan, Yan Yang
Increasing evidence has shown that type 2 diabetes (T2D) is a risk factor for Alzheimer's disease. Neurofibrillary tangles, which consist of hyperphosphorylated tau and misfolded microtubules, is one of the neuropathological hallmarks of Alzheimer's disease. Db/db mice, a rodent model of T2D, also exhibited age-dependent tau hyperphosphorylation. Glucagon-like peptide-1 (GLP-1) mimetics, a type of drug used in T2D, has been found to have neuroprotective effects. The aim of this study was to explore the potential effects of liraglutide (a GLP-1 analog), or insulin, on tau phosphorylation in T2D animals...
October 2015: Journal of Neurochemistry
https://www.readbyqxmd.com/read/26141845/neuroprotective-effects-of-lixisenatide-and-liraglutide-in-the-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-mouse-model-of-parkinson-s-disease
#19
W Liu, J Jalewa, M Sharma, G Li, L Li, C Hölscher
Glucagon-like peptide 1 (GLP-1) is a growth factor. GLP-1 mimetics are on the market as treatments for type 2 diabetes and are well tolerated. These drugs have shown neuroprotective properties in animal models of neurodegenerative disorders. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in animal models of Parkinson's disease (PD), and a clinical trial in PD patients showed promising first results. Liraglutide and lixisenatide are two newer GLP-1 mimetics which have a longer biological half-life than exendin-4...
September 10, 2015: Neuroscience
https://www.readbyqxmd.com/read/26131323/gut-brain-connection-the-neuroprotective-effects-of-the-anti-diabetic-drug-liraglutide
#20
REVIEW
Emanuel Monteiro Candeias, Inês Carolina Sebastião, Susana Maria Cardoso, Sónia Catarina Correia, Cristina Isabel Carvalho, Ana Isabel Plácido, Maria Sancha Santos, Catarina Resende Oliveira, Paula Isabel Moreira, Ana Isabel Duarte
Long-acting glucagon-like peptide-1 (GLP-1) analogues marketed for type 2 diabetes (T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain. This gut secreted hormone plays a potent insulinotropic activity and an important role in maintaining glucose homeostasis. Furthermore, growing evidences suggest the occurrence of several commonalities between T2D and neurodegenerative diseases, insulin resistance being pointed as a main cause for cognitive decline and increased risk to develop dementia...
June 25, 2015: World Journal of Diabetes
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