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Liraglutide alzheimers

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
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
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
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
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...
October 20, 2016: Molecular Neurobiology
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
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
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
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
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
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
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
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
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
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
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
P L McClean, V Parthsarathy, E Faivre, C Hölscher
No abstract text is available yet for this article.
September 9, 2010: Regulatory Peptides
Henrik H Hansen, Katrine Fabricius, Pernille Barkholt, Michael L Niehoff, John E Morley, Jacob Jelsing, Charles Pyke, Lotte Bjerre Knudsen, Susan A Farr, Niels Vrang
Recent studies indicate that glucagon-like peptide 1 (GLP-1) receptor agonists, currently used in the management of type 2 diabetes, exhibit neurotrophic and neuroprotective effects in amyloid-β (Aβ) toxicity models of Alzheimer's disease (AD). We investigated the potential pro-cognitive and neuroprotective effects of the once-daily GLP-1 receptor agonist liraglutide in senescence-accelerated mouse prone 8 (SAMP8) mice, a model of age-related sporadic AD not dominated by amyloid plaques. Six-month-old SAMP8 mice received liraglutide (100 or 500 μg/kg/day, s...
2015: Journal of Alzheimer's Disease: JAD
Angela Greene, Jaclynn Ng, Luz Shepherd, Katherine Carey
Alzheimer's disease (AD) is a progressive neurodegenerative condition primarily affecting individuals 65 years of age and older. There are few therapies available, and the disease is eventually fatal. Although the molecular mechanisms responsible for the development of AD remain unknown, a strong correlation between insulin dysfunction in type 2 diabetes mellitus and AD has recently been established. This has led to innovative research in the prevention and treatment of AD. Currently the most promising antidiabetic treatment options for AD are intranasal insulin and liraglutide, both of which are being investigated in ongoing clinical trials...
February 2015: Consultant Pharmacist: the Journal of the American Society of Consultant Pharmacists
Andrea Špolcová, Barbora Mikulášková, Martina Holubová, Veronika Nagelová, Zdenko Pirnik, Jana Zemenová, Martin Haluzík, Blanka Železná, Marie-Christine Galas, Lenka Maletínská
Numerous epidemiological and experimental studies have demonstrated that patients who suffer from metabolic disorders, such as type 2 diabetes mellitus (T2DM) or obesity, have higher risks of cognitive dysfunction and of Alzheimer's disease (AD). Impaired insulin signaling in the brain could contribute to the formation of neurofibrillary tangles, which contain an abnormally hyperphosphorylated tau protein. This study aimed to determine whether potential tau hyperphosphorylation could be detected in an obesity-induced pre-diabetes state and whether anorexigenic agents could affect this state...
2015: Journal of Alzheimer's Disease: JAD
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