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Insulin AND amyloid

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https://www.readbyqxmd.com/read/27911310/cholinergic-modification-of-neurogenesis-and-gliosis-improves-the-memory-of%C3%A2-a%C3%AE-ppswe-psen1de9-alzheimer-s-disease-model-mice-fed-a-high-fat-diet
#1
Takeshi Matsuda, Tatsuhiro Hisatsune
We previously reported that neuroinflammation contributes to the amnesia of AβPPswe/PSEN1dE9 Alzheimer's disease model mice fed a high-fat diet to induce type-2 diabetes (T2DM-AD mice), but the underlying mechanism for the memory decline remained unclear. Recent studies have suggested that cholinergic modulation is involved in neuroinflammatory cellular reactions including neurogenesis and gliosis, and in memory improvement. In this study, we administered a broad-spectrum cholinesterase inhibitor, rivastigmine (2 mg/kg/day, s...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27905353/-twenty-five-years-of-the-amyloid-hypothesis-of-alzheimer-disease-advances-failures-and-new-perspectives
#2
O S Levin, E E Vasenina
Amyloid hypothesis of Alzheimer's disease (AD) has been long the primary one. During the 25-year history the concept has been dramatically changed. Accumulation of β-amyloid is associated not only with the disruption of its synthesis (as it seemed after the discovery of genetic mechanisms of some familial cases of AD) but rather with the disruption of its clearance and elimination from the brain tissue via the microcirculatory system. It has been recognized that soluble oligomers of β-amyloid, but not senile plaques that consisted of insoluble conjugates described by A...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/27889205/structural-analysis-of-multi-component-amyloid-systems-by-chemometric-saxs-data-decomposition
#3
Fátima Herranz-Trillo, Minna Groenning, Andreas van Maarschalkerweerd, Romà Tauler, Bente Vestergaard, Pau Bernadó
Formation of amyloids is the hallmark of several neurodegenerative pathologies. Structural investigation of these complex transformation processes poses significant experimental challenges due to the co-existence of multiple species. The additive nature of small-angle X-ray scattering (SAXS) data allows for probing the evolution of these mixtures of oligomeric states, but the decomposition of SAXS data into species-specific spectra and relative concentrations is burdened by ambiguity. We present an objective SAXS data decomposition method by adapting the multivariate curve resolution alternating least squares (MCR-ALS) chemometric method...
November 9, 2016: Structure
https://www.readbyqxmd.com/read/27887985/insulin-like-growth-factor-1-protects-sh-sy5y-cells-against-%C3%AE-amyloid-induced-apoptosis-via-the-pi3k-akt-nrf2-pathway
#4
Zigao Wang, Lu Xiong, Guanqun Wang, Wenbin Wan, Chunjiu Zhong, Hengbing Zu
Insulin-like growth factor-1 (IGF-1) shows protective effect against Aβ-induced cytotoxicity and apoptosis, but the underlying mechanisms are poorly characterized. The present study was conducted to explore the mechanisms involved in the beneficial effect of IGF-1 against Aβ-induced apoptosis in SH-SY5Y cells. We found that pretreatment with IGF-1 attenuated Aβ25-35-induced loss of cell viability and apoptosis in SH-SY5Y cells in a dose-dependent manner. In addition, IGF-1 inhibited the generation of reactive oxygen species (ROS) and increased the antioxidant activity in Aβ25-35-treated cells...
November 22, 2016: Experimental Gerontology
https://www.readbyqxmd.com/read/27884163/chronic-adiponectin-deficiency-leads-to-alzheimer-s-disease-like-cognitive-impairments-and-pathologies-through-ampk-inactivation-and-cerebral-insulin-resistance-in-aged-mice
#5
Roy Chun-Laam Ng, On-Yin Cheng, Min Jian, Jason Shing-Cheong Kwan, Philip Wing-Lok Ho, Kenneth King-Yip Cheng, Patrick Ka Kit Yeung, Lena Lei Zhou, Ruby Lai-Chong Hoo, Sookja Kim Chung, Aimin Xu, Karen Siu-Ling Lam, Koon Ho Chan
BACKGROUND: Insulin resistance is the major pathogenesis underlying type 2 diabetes mellitus (T2DM) and these patients have doubled risk of Alzheimer's disease (AD). Increasing evidence suggests that insulin resistance plays an important role in AD pathogenesis, possibly due to abnormal GSK3β activation, causing intra- and extracellular amyloid-beta (Aβ) accumulation. Adiponectin (APN) is an adipokine with insulin-sensitizing and anti-inflammatory effects. Reduced circulatory APN level is associated with insulin resistance and T2DM...
November 25, 2016: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/27866224/the-beneficial-effects-of-empagliflozin-an-sglt2-inhibitor-on-atherosclerosis-in-apoe-mice-fed-a-western-diet
#6
Ji Hye Han, Tae Jung Oh, Ghayoung Lee, Hyo Jin Maeng, Dong Hwa Lee, Kyoung Min Kim, Sung Hee Choi, Hak Chul Jang, Hye Seung Lee, Kyong Soo Park, Young-Bum Kim, Soo Lim
AIMS/HYPOTHESIS: A recent large clinical study has shown that empagliflozin has a lower rate of cardiovascular and all-cause mortality when compared with placebo in patients with type 2 diabetes. We investigated the effect of empagliflozin (compared with glimepiride) on the progression of atherosclerosis, and its possible mechanisms of action. METHODS: Forty-eight 5-week-old male ApoE (-/-) mice were fed a western diet for 20 weeks and divided into four groups: control (saline, 154 mmol/l NaCl), glimepiride 0...
November 19, 2016: Diabetologia
https://www.readbyqxmd.com/read/27865831/rutin-suppresses-human-amylin-hiapp-misfolding-and-oligomer-formation-in-vitro-and-ameliorates-diabetes-and-its-impacts-in-human-amylin-hiapp-transgenic-mice
#7
Jacqueline F Aitken, Kerry M Loomes, Isabel Riba-Garcia, Richard D Unwin, Gordana Prijic, Ashley S Phillips, Anthony R J Phillips, Donghai Wu, Sally D Poppitt, Ke Ding, Perdita E Barran, Andrew W Dowsey, Garth J S Cooper
Pancreatic islet β-cells secrete the hormones insulin and amylin, and defective β-cell function plays a central role in the pathogenesis of type-2 diabetes (T2D). Human amylin (hA, also termed hIAPP) misfolds and forms amyloid aggregates whereas orthologous mouse amylin does neither. Furthermore, hA elicits apoptosis in cultured β-cells and β-cell death in ex-vivo islets. In addition, hA-transgenic mice that selectively express hA in their β-cells, manifest β-cell apoptosis and progressive islet damage that leads to diabetes closely resembling that in patients with T2D...
November 16, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27863851/long-term-exposition-to-a-high-fat-diet-favors-the-appearance-of-%C3%AE-amyloid-depositions-in-the-brain-of-c57bl-6j-mice-a-potential-model-of-sporadic-alzheimer-s-disease
#8
Oriol Busquets, Miren Ettcheto, Mercè Pallàs, Carlos Beas-Zarate, Ester Verdaguer, Carme Auladell, Jaume Folch, Antoni Camins
AIMS: The sporadic and late-onset form of Alzheimer's disease (AD) constitutes the most common form of dementia. This non-familiar form could be a consequence of metabolic syndrome, characterized by obesity and the development of a brain-specific insulin resistance known as type III diabetes. This work demonstrates the development of a significant AD-like neuropathology due to these metabolic alterations. METHODS: C57BL/6J mice strain were divided into two groups, one fed with a diet rich in palmitic acid (high-fat diet, HFD) since their weaning until 16 months of age, and another group used as a control with a regular diet...
November 15, 2016: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/27852778/the-effects-of-peripheral-and-central-high-insulin-on-brain-insulin-signaling-and-amyloid-%C3%AE-in-young-and-old-app-ps1-mice
#9
Molly Stanley, Shannon L Macauley, Emily E Caesar, Lauren J Koscal, Will Moritz, Grace O Robinson, Joseph Roh, Jennifer Keyser, Hong Jiang, David M Holtzman
: Hyperinsulinemia is a risk factor for late-onset Alzheimer's disease (AD). In vitro experiments describe potential connections between insulin, insulin signaling, and amyloid-β (Aβ), but in vivo experiments are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving APPswe/PS1dE9 transgenic mice. Both a postprandial and supraphysiological insulin clamp significantly increased interstitial fluid (ISF) and plasma Aβ compared with controls...
November 16, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27834125/role-of-ageing-and-oxidative-stress-in-regulation-of-amyloid-degrading-enzymes-and-development-of-neurodegeneration
#10
Natalia N Nalivaeva, Anthony J Turner
The accumulation of cerebral amyloid β-peptide (Aβ) is a key precipitating factor for neuronal cell death in Alzheimer's disease (AD). However, brain Aβ levels are modifiable since there is a balance between its formation from the amyloid precursor protein (APP) and its removal by clearance mechanisms, which can be either through proteolysis or by protein binding and subsequent transport). Among the major enzymes degrading brain Aβ are several zinc-proteases: neprilysin (NEP), its homologues NEP2 and the endothelin converting enzymes (ECE-1 and -2) and also the insulin-degrading enzyme (IDE)...
November 10, 2016: Current Aging Science
https://www.readbyqxmd.com/read/27817134/insulin-like-growth-factor-binding-protein-2-interactions-with-alzheimer-s-disease-biomarkers
#11
Elizabeth M Lane, Timothy J Hohman, Angela L Jefferson
Plasma levels of insulin-like growth factor binding protein-2 (IGFBP-2) have been associated with Alzheimer's disease (AD) and brain atrophy. Some evidence suggests a potential synergistic effect of IGFBP-2 and AD neuropathology on neurodegeneration, while other evidence suggests the effect of IGFBP-2 on neurodegeneration is independent of AD neuropathology. Therefore, the current study investigated the interaction between plasma IGFBP-2 and cerebrospinal fluid (CSF) biomarkers of AD neuropathology on hippocampal volume and cognitive function...
November 5, 2016: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/27813426/eicosapentaenoic-acid-and-docosahexaenoic-acid-increase-the-degradation-of-amyloid-%C3%AE-by-affecting-insulin-degrading-enzyme
#12
Marcus O W Grimm, Janine Mett, Christoph P Stahlmann, Viola J Haupenthal, Tamara Blümel, Hannah Stötzel, Heike S Grimm, Tobias Hartmann
Omega-3 polyunsaturated fatty acids (PUFAs) have been proposed to be highly beneficial in Alzheimer's disease (AD). AD pathology is closely linked to an overproduction and accumulation of amyloid-β (Aβ) peptides as extracellular senile plaques in the brain. Total Aβ levels are not only dependent on its production by proteolytic processing of the amyloid precursor protein (APP), but also on Aβ-clearance mechanisms, including Aβ-degrading enzymes. Here we show that the omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) increase Aβ-degradation by affecting insulin-degrading enzyme (IDE), the major Aβ-degrading enzyme secreted into the extracellular space of neuronal and microglial cells...
December 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/27813296/simple-method-to-introduce-an-ester-infrared-probe-into-proteins
#13
Ismail A Ahmed, Feng Gai
The ester carbonyl stretching vibration has recently been shown to be a sensitive and convenient infrared (IR) probe of protein electrostatics due to the linear dependence of its frequency on local electric field. While an ester moiety can be easily incorporated into peptides via solid-phase synthesis, currently there is no method available to site-specifically incorporate it into a large protein. Herein, we show that it is possible to use a cysteine alkylation reaction to achieve this goal and demonstrate the feasibility of this simple method by successfully incorporating a methyl ester group (-CH2 COOCH3 ) into a model peptide (YGGCGG), two amyloid-forming peptides derived from the insulin B chain and Aβ, and bovine serum albumin (BSA)...
November 4, 2016: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/27812546/%C3%AE-cell-specific-increased-expression-of-calpastatin-prevents-diabetes-induced-by-islet-amyloid-polypeptide-toxicity
#14
Tatyana Gurlo, Safia Costes, Jonathan D Hoang, Jacqueline F Rivera, Alexandra E Butler, Peter C Butler
The islet in type 2 diabetes (T2D) shares many features of the brain in protein misfolding diseases. There is a deficit of β cells with islet amyloid derived from islet amyloid polypeptide (IAPP), a protein coexpressed with insulin. Small intracellular membrane-permeant oligomers, the most toxic form of IAPP, are more frequent in β cells of patients with T2D and rodents expressing human IAPP. β Cells in T2D, and affected cells in neurodegenerative diseases, share a comparable pattern of molecular pathology, including endoplasmic reticulum stress, mitochondrial dysfunction, attenuation of autophagy, and calpain hyperactivation...
November 3, 2016: JCI Insight
https://www.readbyqxmd.com/read/27810390/agmatine-ameliorates-type-2-diabetes-induced-alzheimer-s-disease-like-alterations-in-high-fat-diet-fed-mice-via-reactivation-of-blunted-insulin-signalling
#15
Somang Kang, Chul-Hoon Kim, Hosung Jung, Eosu Kim, Ho-Taek Song, Jong Eun Lee
The risk of Alzheimer's disease (AD) is higher in patients with type 2 diabetes mellitus (T2DM). Previous studies in high-fat diet-induced AD animal models have shown that brain insulin resistance in these animals leads to the accumulation of amyloid beta (Aβ) and the reduction in GSK-3β phosphorylation, which promotes tau phosphorylation to cause AD. No therapeutic treatments that target AD in T2DM patients have yet been discovered. Agmatine, a primary amine derived from l-arginine, has exhibited anti-diabetic effects in diabetic animals...
October 31, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27809235/protective-effect-of-genistein-against-neuronal-degeneration-in-apoe-mice-fed-a-high-fat-diet
#16
Yoon-Jin Park, Je Won Ko, Sookyoung Jeon, Young Hye Kwon
Altered cholesterol metabolism is believed to play a causal role in major pathophysiological changes in neurodegeneration. Several studies have demonstrated that the absence of apolipoprotein E (ApoE), a predominant apolipoprotein in the brain, leads to an increased susceptibility to neurodegeneration. Previously, we observed that genistein, a soy isoflavone, significantly alleviated apoptosis and tau hyperphosphorylation in SH-SY5Y cells. Therefore, we investigated the neuroprotective effects of dietary genistein supplementation (0...
October 31, 2016: Nutrients
https://www.readbyqxmd.com/read/27804051/receptor-mediated-toxicity-of-human-amylin-fragment-aggregated-by-short-and-long-term-incubations-with-copper-ions
#17
Giuseppe Caruso, Donatella A Distefano, Paolo Parlascino, Claudia G Fresta, Giuseppe Lazzarino, Susan M Lunte, Vincenzo G Nicoletti
Human amylin (hA1-37) is a polypeptide hormone secreted in conjunction with insulin from the pancreatic β-cells involved in the pathogenesis of type 2 diabetes mellitus (T2DM). The shorter fragment hA17-29 than full-length peptide is capable to form amyloids "in vitro". Here, we monitored the time course of hA17-29 β-amyloid fibril and oligomer formation [without and with copper(II)], cellular toxicity of different amyloid aggregates, and involvement of specific receptors (receptor for advanced glycation end-products, RAGE; low-affinity nerve growth factor receptor, p75-NGFR) in aggregate toxicity...
November 1, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27802879/an-insulin-iapp-hybrid-peptide-is-an-endogenous-antigen-for-cd4-t-cells-in-the-non-obese-diabetic-mouse
#18
Timothy A Wiles, Thomas Delong, Rocky L Baker, Brenda Bradley, Gene Barbour, Roger L Powell, Nichole Reisdorph, Kathryn Haskins
BDC-6.9, a diabetogenic CD4 T cell clone isolated from a non-obese diabetic (NOD) mouse, responds to pancreatic islet cells from NOD but not BALB/c mice. We recently reported that a hybrid insulin peptide (HIP), 6.9HIP, formed by linkage of an insulin C-peptide fragment and a fragment of islet amyloid polypeptide (IAPP), is the antigen for BDC-6.9. We report here that the core 12-mer peptide from 6.9HIP, centered on the hybrid peptide junction, is also highly antigenic for BDC-6.9. In agreement with the observation that BALB/c islet cells fail to stimulate the T cell clone, a single amino acid difference in the BALB/c IAPP sequence renders the BALB/c version of the HIP only weakly antigenic...
October 29, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27802221/sh2b1-is-involved-in-the-accumulation-of-amyloid-%C3%AE-42-in-alzheimer-s-disease
#19
Yijun Shen, Yiling Xia, Shiquan Meng, Nastasia K H Lim, Wenan Wang, Fude Huang
Alzheimer's disease (AD) is characterized by deficits in learning and memory abilities, as well as pathological changes of amyloid-β (Aβ) plaque and neurofibrillary tangle formation in the brain. Insulin has been identified as a modulator of the neuronal pathways involved in learning and memory, and is also implicated as a modulator of Aβ and tau metabolism. Disrupted insulin signaling pathways are evident in AD patients and it is understood that type 2 diabetes can increase the risk of developing AD, suggesting a possible link between metabolic disorders and neurodegeneration...
November 19, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27776993/lixisenatide-attenuates-the-detrimental-effects-of-amyloid-%C3%AE-protein-on-spatial-working-memory-and-hippocampal-neurons-in-rats
#20
Hong-Yan Cai, Zhao-Jun Wang, Christian Hölscher, Li Yuan, Jun Zhang, Peng Sun, Jing Li, Wei Yang, Mei-Na Wu, Jin-Shun Qi
Type 2 diabetes mellitus(T2DM) is a risk factor of Alzheimer's disease (AD), which is most likely linked to impairments of insulin signaling in the brain. Hence, drugs enhancing insulin signaling may have therapeutic potential for AD. Lixisenatide, a novel long-lasting glucagon-like peptide 1 (GLP-1) analogue, facilitates insulin signaling and has neuroprotective properties. We previously reported the protective effects of lixisenatide on memory formation and synaptic plasticity. Here, we describe additional key neuroprotective properties of lixisenatide and its possible molecular and cellular mechanisms against AD-related impairments in rats...
October 21, 2016: Behavioural Brain Research
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