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Insulin AND amyloid

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https://www.readbyqxmd.com/read/28078611/hyperbaric-oxygen-prevents-cognitive-impairments-in-mice-induced-by-d-galactose-by-improving-cholinergic-and-anti-apoptotic-functions
#1
Chunxia Chen, Luying Huang, Zhihuan Nong, Yaoxuan Li, Wan Chen, Jianping Huang, Xiaorong Pan, Guangwei Wu, Yingzhong Lin
Our previous study demonstrated that hyperbaric oxygen (HBO) improved cognitive impairments mainly by regulating oxidative stress, inflammatory responses and aging-related gene expression. However, a method for preventing cognitive dysfunction has yet to be developed. In the present study, we explored the protective effects of HBO on the cholinergic system and apoptosis in D-galactose (D-gal)-treated mice. A model of aging was established via systemic intraperitoneal injection of D-gal daily for 8 weeks. HBO was administered during the last 2 weeks of D-gal injection...
January 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28071890/peptide-conjugates-of-benzene-carboxylic-acids-as-agonists-and-antagonists-of-amylin-aggregation
#2
Ruel Z B Desamero, Adam A Profit, Jayson Del Rosario Vedad
Human islet amyloid polypeptide (hIAPP), also known as amylin, is a 37 residue peptide hormone that is stored and co-secreted with insulin. hIAPP plays a pivotal role in type 2 diabetes and is the major component of amyloid deposits found in the pancreas of patients afflicted with the disease. The self-assembly of hIAPP and the formation of amyloid is linked to the death of insulin producing -cells. Recent findings suggest soluble hIAPP oligomers are the cytotoxic species responsible for -cell loss whereas amyloid fibrils themselves may indeed be innocuous...
January 10, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28070499/metabolic-relationship-between-diabetes-and-alzheimer-s-disease-affected-by-cyclo-his-pro-plus-zinc-treatment
#3
REVIEW
Moon K Song, David S Bischoff, Albert M Song, Koichi Uyemura, Dean T Yamaguchi
BACKGROUND: Association of Alzheimer's Disease (AD) with Type 2 Diabetes (T2D) has been well established. Cyclo(His-Pro) plus zinc (Cyclo-Z) treatment ameliorated diabetes in rats and similar improvements have been seen in human patients. Treatment of amyloid precursor protein (APP) transgenic mice with Cyclo-Z exhibited memory improvements and significantly reduced Aβ-40 and Aβ-42 protein levels in the brain tissues of the mice. SCOPE OF REVIEW: Metabolic relationship between AD and T2D will be described with particular attention to insulin sensitivity and Aβ degradation in brain and plasma tissues...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28069203/drastic-acceleration-of-fibrillation-of-insulin-by-transient-cavitation-bubble
#4
Kichitaro Nakajima, Daisuke Nishioka, Masahiko Hirao, Masatomo So, Yuji Goto, Hirotsugu Ogi
Amyloid-fibril formation of proteins can be accelerated by ultrasonic irradiation to the peptide solutions. Although this phenomenon contributes to understanding pathogenic behavior of amyloidosis, its physical mechanism has not been clarified, because several factors (cavitation, temperature increase, stirring effect, and so on) related to ultrasonic irradiation can participate in the fibrillation reaction. Here, we independently study contributions of the possible factors, using insulin, which is extremely stable and then suitable for the mechanism clarification...
May 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28054630/disaggregation-of-amylin-aggregate-by-novel-conformationally-restricted-aminobenzoic-acid-containing-%C3%AE-%C3%AE-and-%C3%AE-%C3%AE-hybrid-peptidomimetics
#5
Ashim Paul, Sourav Kalita, Sujan Kalita, Piruthivi Sukumar, Bhubaneswar Mandal
Diabetes has emerged as a threat to the current world. More than ninety five per cent of all the diabetic population has type 2 diabetes mellitus (T2DM). Aggregates of Amylin hormone, which is co-secreted with insulin from the pancreatic β-cells, inhibit the activities of insulin and glucagon and cause T2DM. Importance of the conformationally restricted peptides for drug design against T2DM has been invigorated by recent FDA approval of Symlin, which is a large conformationally restricted peptide. However, Symlin still has some issues including solubility, oral bioavailability and cost of preparation...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28049400/elucidating-treatment-of-alzheimer-s-disease-via-different-receptors
#6
Badar Ul Islam, Mohd Shahnawaz Khan, Nasimudeen R Jabir, Mohammad Amjad Kamal, Shams Tabrez
Alzheimer's disease (AD) is an irreversible multifaceted neurodegenerative disorder that gradually degrades neuronal cells. Presently, it is the most common reason for the memory loss and dementia in older individuals. It is patho-physiologically described by extracellular amyloid beta (Aβ) deposition, intracellular neurofibrillary tangles (NFTs) retention, neuronal decline, and neurotransmitter system derangement. Various receptors such as nicotinic acetylcholine, N-methyl-D-aspartate, insulin, serotonin, adenosine, and histamine are actively involved in the physiological progression of AD...
January 3, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28043897/natural-products-against-alzheimer-s-disease-pharmaco-therapeutics-and-biotechnological-interventions
#7
REVIEW
Abhijit Dey, Raktim Bhattacharya, Anuradha Mukherjee, Devendra Kumar Pandey
Alzheimer's disease (AD) is a severe, chronic and progressive neurodegenerative disease associated with memory and cognition impairment ultimately leading to death. It is the commonest reason of dementia in elderly populations mostly affecting beyond the age of 65. The pathogenesis is indicated by accumulation of the amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFT) in brain tissues and hyperphosphorylation of tau protein in neurons. The main cause is considered to be the formation of reactive oxygen species (ROS) due to oxidative stress...
December 30, 2016: Biotechnology Advances
https://www.readbyqxmd.com/read/28041733/glucose-requirements-of-an-activated-immune-system-in-lactating-holstein-cows
#8
S K Kvidera, E A Horst, M Abuajamieh, E J Mayorga, M V Sanz Fernandez, L H Baumgard
Accurately quantifying activated immune system energy requirements in vivo is difficult, but a better understanding may advance strategies to maximize animal productivity. Study objectives were to estimate whole-body glucose utilization following an i.v. endotoxin challenge. Lactating Holstein cows were jugular catheterized and assigned 1 of 3 bolus treatments: control (CON; 5 mL of saline; n = 6), lipopolysaccharide (LPS)-administered (LPS-C; 1.5 μg/kg of body weight; Escherichia coli 055:B5; n = 6), and LPS + euglycemic clamp (LPS-Eu; 1...
December 29, 2016: Journal of Dairy Science
https://www.readbyqxmd.com/read/28039031/worsening-of-memory-deficit-induced-by-energy-dense-diet-in-a-rat-model-of-early-alzheimer-s-disease-is-associated-to-neurotoxic-a%C3%AE-species-and-independent-of-neuroinflammation
#9
Pamela V Martino Adami, Pablo Galeano, Marina L Wallinger, Celia Quijano, Alejandro Rabossi, Eleonora S Pagano, Natividad Olivar, Carlos Reyes Toso, Daniel Cardinali, Luis I Brusco, Sonia Do Carmo, Rafael Radi, Goar Gevorkian, Eduardo M Castaño, A Claudio Cuello, Laura Morelli
Diet is a modifiable risk factor for Alzheimer's disease (AD), but the mechanisms linking alterations in peripheral metabolism and cognition remain unclear. Since it is especially difficult to study long-term effects of high-energy diet in individuals at risk for AD, we addressed this question by using the McGill-R-Thy1-APP transgenic rat model (Tg(+/-)) that mimics presymptomatic AD. Wild-type and Tg(+/-) rats were exposed during 6months to a standard diet or a Western diet (WD), high in saturated fat and sugar...
December 27, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28035937/mtorc2-rictor-in-alzheimer-s-disease-and-reversal-of-amyloid-%C3%AE-expression-induced-insulin-resistance-and-toxicity-in-rat-primary-cortical-neurons
#10
Han-Kyu Lee, Bumsup Kwon, Cynthia A Lemere, Suzanne de la Monte, Kyohei Itamura, Austin Y Ha, Henry W Querfurth
Mammalian target of rapamycin complex 1 (mTORC1), a nutrient sensor and central controller of cell growth and proliferation, is altered in various models of Alzheimer's disease (AD). Even less studied or understood in AD is mammalian target of rapamycin complex 2 (mTORC2) that influences cellular metabolism, in part through the regulations of Akt/PKB and SGK. Dysregulation of insulin/PI3K/Akt signaling is another important feature of AD pathogenesis. We found that both total mTORC1 and C2 protein levels and individual C1 and C2 enzymatic activities were decreased in human AD brain samples...
December 30, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28034783/cerebellar-insulin-igf-1-signaling-in-diabetic-rats-effects-of-exercise-training
#11
Mariana Eiras Borges, Alessandra Mussi Ribeiro, José Rodrigo Pauli, Luciana Mendonça Arantes, Eliete Luciano, Leandro Pereira de Moura, José Alexandre Curiacos de Almeida Leme, Alessandra Medeiros, Natália Oliveira Bertolini, Clarice Yoshiko Sibuya, Ricardo José Gomes
The Diabetes Mellitus (DM) is a chronic disease associated with loss of brain regions such as the cerebellum, increasing the risk of developing neurodegenerative diseases such as Parkinson's disease (PD). In the brain of diabetic and PD organisms the insulin/IGF-1 signaling is altered. Exercise training is an effective intervention for the prevention of neurodegerative diseases since it release neurotrophic factors and regulating insulin/IGF-1 signaling in the brain. This study aimed to evaluate the proteins involved in the insulin/IGF-1 pathway in the cerebellum of diabetic rats subjected to exercise training protocol...
December 26, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/28025127/glucose-tolerance-and-insulin-sensitivity-are-impaired-in-app-ps1-transgenic-mice-prior-to-amyloid-plaque-pathogenesis-and-cognitive-decline
#12
Lauren Macklin, Chelsea M Griffith, Yan Cai, Gregory M Rose, Xiao-Xin Yan, Peter R Patrylo
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by beta-amyloid (Aβ) deposition, neurofibrillary tangles and cognitive decline. Clinical data suggests that both type 1 and type 2 diabetes are risk factors for AD-related dementia and several clinical studies have demonstrated that AD patients show alterations in peripheral glucose regulation characterized by insulin resistance (hyperinsulinemia) or hypoinsulinemia. Whether animal models of AD exhibit a pre-diabetic phenotype without additional dietary or experimental manipulation is unclear however, with contradictory data available...
December 23, 2016: Experimental Gerontology
https://www.readbyqxmd.com/read/28017127/marginal-vitamin-a-deficiency-exacerbates-memory-deficits-following-a%C3%AE-1-42-injection-in-rats
#13
Jiaying Zeng, Tingyu Li, Ming Gong, Wei Jiang, Ting Yang, Jie Chen
BACKGROUND: Although clinical vitamin A deficiency (VAD), which is a public health problem throughout the developing world, has been well controlled, marginal vitamin A deficiency (MVAD) is far more prevalent, especially among pregnant women and preschool children in China. Increasing evidence suggests that VAD is involved in the pathogenesis of Alzheimer's disease (AD). However, whether MVAD, beginning early in life, increases the risk of developing AD has yet to be determined. OBJECTIVE: The goal of this study was to investigate the long-term effects of MVAD on the pathogenesis of AD in rats...
December 23, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/28008970/high-resolution-spectroscopy-reveals-fibrillation-inhibition-pathways-of-insulin
#14
Tanja Deckert-Gaudig, Volker Deckert
Fibril formation implies the conversion of a protein's native secondary structure and is associated with several neurodegenerative diseases. A better understanding of fibrillation inhibition and fibril dissection requires nanoscale molecular characterization of amyloid structures involved. Tip-enhanced Raman scattering (TERS) has already been used to chemically analyze amyloid fibrils on a sub-protein unit basis. Here, TERS in combination with atomic force microscopy (AFM), and conventional Raman spectroscopy characterizes insulin assemblies generated during inhibition and dissection experiments in the presence of benzonitrile, dimethylsulfoxide, quercetin, and β-carotene...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28000098/insulin-formulation-characterization-the-thioflavin-t-assays
#15
Morten Schlein
The insulin molecule was discovered in 1921. Shortly thereafter, its propensity towards amyloid fibril formation, fibrillation, was observed and described in the literature as a "precipitate." In the past decades, the increased incidence of type 2 diabetes has reached global epidemic proportions. This has emphasized the demands for both insulin production and the development of modern insulin products for unmet medical needs. Bringing such new insulin drug products to the market for the benefit of patients requires that many CMC-related processes are understood, described, and controlled...
December 20, 2016: AAPS Journal
https://www.readbyqxmd.com/read/27999871/loss-of-prohormone-convertase-2-promotes-beta-cell-dysfunction-in-a-rodent-transplant-model-expressing-human-pro-islet-amyloid-polypeptide
#16
Jaques A Courtade, Evan Y Wang, Paul Yen, Derek L Dai, Galina Soukhatcheva, Paul C Orban, C Bruce Verchere
AIMS/HYPOTHESIS: A contributor to beta cell failure in type 2 diabetes and islet transplants is amyloid formation by aggregation of the beta cell peptide, islet amyloid polypeptide (IAPP). Similar to the proinsulin processing pathway that generates insulin, IAPP is derived from a prohormone precursor, proIAPP, which requires cleavage by prohormone convertase (PC) 1/3 and PC2 in rodent pancreatic beta cells. We hypothesised that loss of PC2 would promote beta cell death and dysfunction in a rodent model of human beta cell proIAPP overexpression...
December 20, 2016: Diabetologia
https://www.readbyqxmd.com/read/27999295/special-issue-molecules-against-alzheimer
#17
EDITORIAL
Michael Decker, Diego Muñoz-Torrero
This Special Issue, entitled "Molecules against Alzheimer", gathers a number of original articles, short communications, and review articles on recent research efforts toward the development of novel drug candidates, diagnostic agents and therapeutic approaches for Alzheimer's disease (AD), the most prevalent neurodegenerative disorder and a leading cause of death worldwide. This Special Issue contains many interesting examples describing the design, synthesis, and pharmacological profiling of novel compounds that hit one or several key biological targets, such as cholinesterases, β-amyloid formation or aggregation, monoamine oxidase B, oxidative stress, biometal dyshomeostasis, mitochondrial dysfunction, serotonin and/or melatonin systems, the Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase, or nuclear erythroid 2-related factor...
December 16, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27997158/chaperone-like-activity-of-calnuc-prevents-amyloid-aggregation
#18
Madhavi Kanuru, Gopala Krishna Aradhyam
Calnuc is a ubiquitously expressed protein of the EF-hand Ca(2+)-binding superfamily. Previous studies have implicated it in Ca(2+)-sensitive physiological processes, whereas details of its function and involvement in human diseases are lacking. Drawing upon the sequence homology of calnuc with calreticulin, we propose it functions as a molecular chaperone-like protein. In cells under thermal, chemical [urea and guanidinium chloride (GdmCl)], and acidic stress, calnuc exhibits properties similar to those of established chaperone-like proteins (GRP78, spectrin, and α-crystallin), effectively demonstrated by its ability to suppress aggregation of malate dehydrogenase (MDH), alcohol dehydrogenase, and catalase...
December 20, 2016: Biochemistry
https://www.readbyqxmd.com/read/27988872/insulin-resistance-and-neurodegeneration-progress-towards-the-development-of-new-therapeutics-for-alzheimer-s-disease
#19
REVIEW
Suzanne M de la Monte
Alzheimer's disease (AD) should be regarded as a degenerative metabolic disease caused by brain insulin resistance and deficiency, and overlapping with the molecular, biochemical, pathophysiological, and metabolic dysfunctions in diabetes mellitus, non-alcoholic fatty liver disease, and metabolic syndrome. Although most of the diagnostic and therapeutic approaches over the past several decades have focused on amyloid-beta (Aβ42) and aberrantly phosphorylated tau, which could be caused by consequences of brain insulin resistance, the broader array of pathologies including white matter atrophy with loss of myelinated fibrils and leukoaraiosis, non-Aβ42 microvascular disease, dysregulated lipid metabolism, mitochondrial dysfunction, astrocytic gliosis, neuro-inflammation, and loss of synapses vis-à-vis growth of dystrophic neurites, is not readily accounted for by Aβ42 accumulations, but could be explained by dysregulated insulin/IGF-1 signaling with attendant impairments in signal transduction and gene expression...
December 17, 2016: Drugs
https://www.readbyqxmd.com/read/27982586/toward-allosterically-increased-catalytic-activity-of-insulin-degrading-enzyme-against-amyloid-peptides
#20
Igor V Kurochkin, Enrico Guarnera, Jin H Wong, Frank Eisenhaber, Igor N Berezovsky
The physiological role of insulin-degrading enzyme (IDE) in the intracytosolic clearance of amyloid β (Aβ) and other amyloid-like peptides supports a hypothesis that human IDE hyperactivation could be therapeutically beneficial for the treatment of late-onset Alzheimer's disease (AD). The major challenge standing in the way of this goal is increasing the specific catalytic activity of IDE against the Aβ substrate. There were previous indications that the allosteric mode of IDE activity regulation could potentially provide a highly specific path toward degradation of amyloid-like peptides, while not dramatically affecting activity against other substrates...
December 16, 2016: Biochemistry
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