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Insulin AND amyloid

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https://www.readbyqxmd.com/read/29782959/targeting-central-%C3%AE-2-receptors-ameliorates-streptozotocin-induced-neuroinflammation-via-inhibition-of-glycogen-synthase-kinase3-pathway-in-mice
#1
Nora O Abdel Rasheed, Nesrine S El-Sayed, Aiman S El-Khatib
Alzheimer's disease (AD) is portrayed by progressive cognitive decline and pathological deposition of amyloid plaques as well as neurofibrillary tangles. Most of AD cases are sporadic, resulting from overlap of various environmental and genetic factors. Intra-cerebroventricular injection of streptozotocin (STZ) leads to insulin resistance brain state accompanied by memory decline, oxidative stress, and neuro-degeneration which mimic the pathologies associated with sporadic Alzheimer's disease (SAD). In the current study, protective effects of formoterol in STZ-induced SAD were studied...
May 18, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29780554/mechanistic-perspective-and-functional-activity-of-insulin-in-amylin-aggregation
#2
Michal Baram, Sharon Gilead, Ehud Gazit, Yifat Miller
Insulin is a key regulatory polypeptide that is secreted from pancreatic β-cells and has several important effects on the synthesis of lipids, regulation of enzymatic activities, blood glucose levels and the prevention of hyperglycemia. Insulin was demonstrated to self-assemble into ordered amyloid fibrils upon repeated injections, although the possible biological significance of the supramolecular structures is enigmatic. Amylin is also an amyloidogenic polypeptide that is secreted from pancreatic β-cells and plays an important role in glycemic regulation preventing post-prandial spikes in blood glucose levels...
May 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29775005/-determination-and-significance-of-serum-mpo-and-amylin-in-adult-patients-with-osahs-after-short-range-noninvasive-positive-pressure-ventilation
#3
X H Chen, P J Chen, Y Long, Q P Huang
Objective: The aim of this study to investigate the determination and significance of serum MPO and amylin in adult patients with OSAHS after short-range noninvasive positive pressure ventilation. Method: Eighty-seven OSAHS patients were divided into severe group (30 cases), moderate group (30 cases) and mild group (27 cases) according to the AHI range. Twenty-seven outpatient health persons were selected as the control group. Serum amylin and myeloperoxidase were measured by ELISA; Amyloid and myeloperoxidase were reassessed in 30 patients with severe OSAHS after 6 months of combined therapy, and the relationship between amylin, myeloperoxidase and PSG was analyzed...
June 5, 2017: Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery
https://www.readbyqxmd.com/read/29755351/gastrodin-attenuates-bilateral-common-carotid-artery-occlusion-induced-cognitive-deficits-via-regulating-a%C3%AE-related-proteins-and-reducing-autophagy-and-apoptosis-in-rats
#4
Bo Liu, Jian-Mei Gao, Fei Li, Qi-Hai Gong, Jing-Shan Shi
Gastrodin (GAS), an active constituent extracted from Gastrodia elata Blume, is used to treat ischemic stroke, epilepsy, dizziness, and dementia for centuries in China. This study examined its effects on vascular dementia (VD) and the underlying molecular mechanisms. VD was established by ligation of bilateral common carotid artery occlusion (BCCAO). A total of 7 days after BCCAO surgery, GAS (15, 30, and 60 mg/kg) was orally administered for 28 consecutive days to evaluate therapeutic effects. Cognitive function was tested by the Morris water maze...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29743868/insulin-resistance-as-a-therapeutic-target-in-the-treatment-of-alzheimer-s-disease-a-state-of-the-art-review
#5
REVIEW
Christian Benedict, Claudia A Grillo
Research in animals and humans has shown that type 2 diabetes and its prodromal state, insulin resistance, promote major pathological hallmarks of Alzheimer's disease (AD), such as the formation of amyloid plaques and neurofibrillary tangles (NFT). Worrisomely, dysregulated amyloid beta (Aβ) metabolism has also been shown to promote central nervous system insulin resistance; although the role of tau metabolism remains controversial. Collectively, as proposed in this review, these findings suggest the existence of a mechanistic interplay between AD pathogenesis and disrupted insulin signaling...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29738527/defensive-effect-of-microrna-200b-c-against-amyloid-beta-peptide-induced-toxicity-in-alzheimer-s-disease-models
#6
Sayuri Higaki, Masashi Muramatsu, Akio Matsuda, Kenji Matsumoto, Jun-Ichi Satoh, Makoto Michikawa, Shumpei Niida
MiRNA molecules are important post-transcriptional regulators of gene expression in the brain function. Altered miRNA profiles could represent a defensive response against the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD). Endogenous miRNAs have lower toxic effects than other gene silencing methods, thus enhancing the expression of defensive miRNA could be an effective therapy. However, little is known about the potential of targeting miRNAs for the treatment of AD. Here, we examined the function of the miR-200 family (miR-200a, -141, -429, -200b, -200c), identified using miRNA microarray analysis of cortical tissue from Tg2576 transgenic mice...
2018: PloS One
https://www.readbyqxmd.com/read/29721854/abscisic-acid-supplementation-rescues-high-fat-diet-induced-alterations-in-hippocampal-inflammation-and-irss-expression
#7
Alberto Ribes-Navarro, Mariam Atef, Sandra Sánchez-Sarasúa, María Teresa Beltrán-Bretones, Francisco Olucha-Bordonau, Ana María Sánchez-Pérez
Accumulated evidence indicates that neuroinflammation induces insulin resistance in the brain. Moreover, both processes are intimately linked to neurodegenerative disorders, including Alzheimer's disease. Potential mechanisms underlying insulin resistance include serine phosphorylation of the insulin receptor substrate (IRS) or insulin receptor (IR) misallocation. However, only a few studies have focused on IRS expression in the brain and its modulation in neuroinflammatory processes. This study used the high-fat diet (HFD) model of neuroinflammation to study the alterations of IR, an insulin-like growth factor receptor (IGF1R) and IRS expressions in the hippocampus...
May 2, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29720669/mixed-bacillus-species-enhance-the-innate-immune-response-and-stress-tolerance-in-yellow-perch-subjected-to-hypoxia-and-air-exposure-stress
#8
Nour Eissa, Han-Ping Wang, Hong Yao, ElSayed Abou-ElGheit
Stress enhances the disease susceptibility in fish by altering the innate immune responses, which are essential defense mechanisms. The use of probiotics is increasingly popular in the aquaculture industry. Yellow perch is a promising candidate for aquaculture. We investigated the efficiency of a mixed Bacillus species in minimizing the potential problems resulting from husbandry practices such as hypoxia and exposure to air in yellow perch. We showed that hypoxia and air exposure conditions induced a significant reduction in the early innate immune response (lysozyme activity, interferon-induced-GTP-binding protein-Mx1 [mx], interleukin-1β [il1β], serum amyloid-A [saa]), and a substantial increase in cortisol, heat shock protein (Hsp70), glutathione peroxidase (Gpx), superoxide dismutase (Sod1) that associated with a decline in insulin-like growth factor-1 (Igf1)...
May 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29710715/targeting-insulin-for-alzheimer-s-disease-mechanisms-status-and-potential-directions
#9
Jung Hyun Lee, Jordan B Jahrling, Larry Denner, Kelly T Dineley
Insulin resistance can occur when the body is unable to respond to insulin even in excess. In the brain, insulin manages glucose metabolism in regions such as the hippocampus and plays a key role in directly regulating ERK, a kinase required for the type of memory compromised in early Alzheimer's disease (AD). Human imaging studies show that brain glucose utilization declines with age and is notably impaired in subjects with early AD. Likewise, animal models of AD or insulin resistance, or both, demonstrate that dysfunctional insulin signaling and insulin resistance in the brain have reciprocity with neuroinflammation and aberrant accumulation of amyloid-β (Aβ), pathological hallmarks in AD...
April 27, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29706312/metabolic-syndrome-marks-early-risk-for-cognitive-decline-with-apoe4-gene-variation-a-case-study
#10
Dawson Brown, Kelly J Gibas
A vast amount of research has been done on the APOE4 genetic marker for Alzheimer's disease (AD), but its connection to metabolic processes associated with peripheral insulin resistance and cerebral glucose metabolism is still relatively unknown. The APOE4 allele is the strongest genetic risk factor for developing late-onset Alzheimer's disease, particularly in individuals who have inherited two copies of the gene (Zhao et al., 2017). In this case study, a 38 year old male with metabolic syndrome (MetS), the APOE4 gene, early stage memory problems and a family history of Alzheimer's Disease (AD) was placed on a ketogenic diet combined with high intensity interval training (HIIT) for 10 weeks...
April 20, 2018: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/29697253/analysis-of-the-role-of-the-conserved-disulfide-in-amyloid-formation-by-human-iapp-in-homogenous-and-heterogeneous-environments
#11
Zachary Ridgway, Xiaoxue Zhang, Amy G Wong, Andisheh Abedini, Ann Marie Schmidt, Daniel P Raleigh
Human islet amyloid polypeptide (hIAPP) is a hormone secreted from β-cells in the Islets of Langerhans in response to the same stimuli that lead to insulin secretion. hIAPP plays an adaptive role in glucose homeostasis, but misfolds to form insoluble, fibrillar aggregates in type-II diabetes that are associated with the disease. Along the misfolding pathway, hIAPP forms species that are toxic to β-cells, resulting in reduced β-cell mass. hIAPP contains a strictly conserved disulfide bond between residues 2-7, which forms a small loop at the N-terminus of the molecule...
April 26, 2018: Biochemistry
https://www.readbyqxmd.com/read/29687202/attenuation-of-aluminum-chloride-induced-neuroinflammation-and-caspase-activation-through-the-akt-gsk-3%C3%AE-pathway-by-hesperidin-in-wistar-rats
#12
Arokiasamy Justin-Thenmozhi, Mathiyazahan Dhivya Bharathi, Ramaraj Kiruthika, Thamilarasan Manivasagam, Anupom Borah, Musthafa Mohamed Essa
Hesperidin, a flavanoglycone abundantly present in citrus fruits, is reported to have antioxidant, anti-inflammatory, and neuroprotective properties. Previous reports from our laboratory indicated the neuroprotective effect of hesperidin against aluminum chloride (AlCl3 )-induced memory loss, acetylcholine esterase hyperactivity, oxidative stress, and enhanced expression of amyloid β protein biosynthesis-related markers. However, their role on AlCl3 -induced inflammation, caspase activation, Tau pathology, altered Akt/GSK 3β signaling pathway, and Aβ clearance marker has not yet been fully elucidated...
April 23, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29682407/kill-two-birds-with-one-stone-making-multi-transgenic-pre-diabetes-mouse-models-through-insulin-resistance-and-pancreatic-apoptosis-pathogenesis
#13
Siyuan Kong, Jinxue Ruan, Kaiyi Zhang, Bingjun Hu, Yuzhu Cheng, Yubo Zhang, Shulin Yang, Kui Li
Background: Type 2 diabetes is characterized by insulin resistance accompanied by defective insulin secretion. Transgenic mouse models play an important role in medical research. However, single transgenic mouse models may not mimic the complex phenotypes of most cases of type 2 diabetes. Methods: Focusing on genes related to pancreatic islet damage, peripheral insulin resistance and related environmental inducing factors, we generated single-transgenic (C/EBP homology protein, CHOP) mice (CHOP mice), dual-transgenic (human islet amyloid polypeptide, hIAPP; CHOP) mice (hIAPP-CHOP mice) and triple-transgenic (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1; hIAPP; CHOP) mice (11β-HSD1-hIAPP- CHOP mice)...
2018: PeerJ
https://www.readbyqxmd.com/read/29674342/app-deficiency-results-in-resistance-to-obesity-but-impairs-glucose-tolerance-upon-high-fat-feeding
#14
Juliane Czeczor, Amanda Genders, Kathryn Aston-Mourney, Timothy Connor, Liam Hall, Kyoko Hasebe, Megan Ellis, Kirstie De Jong, Darren Henstridge, Peter Meikle, Mark Febbraio, Ken Walder, Sean L McGee
The amyloid precursor protein (APP) generates a number of peptides when processed through different cleavage mechanisms, including the Aβ peptide that is implicated in the development of Alzheimer's disease. It is well established that APP via its cleaved peptides regulates aspects of neuronal metabolism. Emerging evidence suggests that amyloidogenic processing of APP can lead to altered systemic metabolism, similar to that observed in metabolic disease states. In the present study, we investigated the effect of APP deficiency on obesity-induced alterations in systemic metabolism...
April 19, 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29668263/neuroprotective-effect-of-alpha-linolenic-acid-against-a%C3%AE-mediated-inflammatory-responses-in-c6-glial-cell
#15
Ah Young Lee, Myoung Hee Lee, Sanghyun Lee, Eun Ju Cho
Therapeutic approaches for neurodegeneration, such as Alzheimer's disease (AD), have been widely studied. One of the critical hallmarks of AD is accumulation of amyloid beta (Aβ). Aβ induces neurotoxicity and releases inflammatory mediators or cytokines through activation of glial cell, and these pathological features are observed in AD patient's brain. The purpose of this study is to investigate the protective effect of alpha-linolenic acid (ALA) on Aβ25-35 -induced neurotoxicity in C6 glial cells. Exposure of C6 glial cells to 50 μM 25-35 caused cell death, over-production of nitric oxide (NO), and pro-inflammatory cytokines release [interleukin (IL)-6 and tumor necrosis factor-α], while treatment of ALA increased cell viability and markedly attenuated Aβ25-35 -induced excessive production of NO and those inflammatory cytokines...
April 18, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29664151/the-receptor-for-advanced-glycation-endproducts-is-a-mediator-of-toxicity-by-iapp-and-other-proteotoxic-aggregates-establishing-and-exploiting-common-ground-for-novel-amyloidosis-therapies
#16
REVIEW
Andisheh Abedini, Julia Derk, Ann Marie Schmidt
Proteotoxicity plays a key role in many devastating human disorders, including Alzheimer's, Huntington's and Parkinson's diseases; type 2 diabetes; systemic amyloidosis; and cardiac dysfunction, to name a few. The cellular mechanisms of proteotoxicity in these disorders have been the focus of considerable research, but their role in prevalent and morbid disorders, such as diabetes, is less appreciated. There is a large body of literature on the impact of glucotoxicity and lipotoxicity on insulin-producing pancreatic β-cells, and there is increasing recognition that proteotoxicty plays a key role...
April 17, 2018: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29663818/alternative-hypotheses-related-to-alzheimer-s-disease
#17
V Cubinkova, B Valachova, I Uhrinova, V Brezovakova, T Smolek, S Jadhav, N Zilka
Alzheimer's disease represents the most common form of dementia and belongs to the group of neurodegenerative disorders characterized by progressive loss of neurons in the central nervous system. In the pathogenesis of Alzheimer's disease several etiologic and pathogenic factors exist, which lead to the dysfunction of neurotransmitter systems and consequent cognitive decline. Last three decades have delivered a crucial progress leading to better understanding of Alzheimer's disease, however, the exact mechanisms of pathology remain unclear...
2018: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/29645399/a%C3%AE-induces-prion-protein-amyloid-formation-evidence-for-widespread-amyloidogenic-effect-of-a%C3%AE
#18
Ryo Honda
Transmissible spongiform encephalopathy (TSE) is associated with misfolding of prion protein (PrP) into an amyloid β-rich aggregate. Previous studies have indicated that PrP interacts with Alzheimer disease amyloid-β peptide (Aβ), but it remains elusive how this interaction impacts on the misfolding of PrP. This study presents the first in vitro evidence that Aβ induces PrP-amyloid formation at submicromolar concentrations. Interestingly, systematic mutagenesis of PrP revealed that Aβ requires no specific amino acid sequences in PrP, and induces the misfolding of other unrelated proteins (insulin and lysozyme) into amyloid fibrils in a manner analogous to PrP...
April 12, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29628040/-patterns-of-brain-ageing
#19
Carlos Fernández Viadero, Rosario Verduga Vélez, Dámaso Crespo Santiago
Neuroplasticity lends the brain a strong ability to adapt to changes in the environment that occur during ageing. Animal models have shown alterations in neurotransmission and imbalances in the expression of neural growth factor. Changes at the morphometric level are not constant. Volume loss is related to alterations in neuroplasticity and involvement of the cerebral neuropil. Although there are no conclusive data, physical exercise improves the molecular, biological, functional and behavioural-cognitive changes associated with brain ageing...
June 2017: Revista Española de Geriatría y Gerontología
https://www.readbyqxmd.com/read/29615609/conformational-switching-within-dynamic-oligomers-underpins-toxic-gain-of-function-by-diabetes-associated-amyloid
#20
Melissa Birol, Sunil Kumar, Elizabeth Rhoades, Andrew D Miranker
Peptide mediated gain-of-toxic function is central to pathology in Alzheimer's, Parkinson's and diabetes. In each system, self-assembly into oligomers is observed and can also result in poration of artificial membranes. Structural requirements for poration and the relationship of structure to cytotoxicity is unaddressed. Here we focus on islet amyloid polypeptide (IAPP) mediated loss-of-insulin secreting cells in patients with diabetes. Newly developed methods enable structure-function enquiry to focus on intracellular oligomers composed of hundreds of IAPP...
April 3, 2018: Nature Communications
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