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https://www.readbyqxmd.com/read/28655134/multiple-mechanisms-linking-type-2-diabetes-and-alzheimer-s-disease-testosterone-as-a-modifier
#1
Prita R Asih, Michelle L Tegg, Hamid Sohrabi, Malcolm Carruthers, Samuel E Gandy, Farid Saad, Giuseppe Verdile, Lars M Ittner, Ralph N Martins
Evidence in support of links between type-2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) has increased considerably in recent years. AD pathological hallmarks include the accumulation of extracellular amyloid-β (Aβ) and intracellular hyperphosphorylated tau in the brain, which are hypothesized to promote inflammation, oxidative stress, and neuronal loss. T2DM exhibits many AD pathological features, including reduced brain insulin uptake, lipid dysregulation, inflammation, oxidative stress, and depression; T2DM has also been shown to increase AD risk, and with increasing age, the prevalence of both conditions increases...
June 22, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28652187/hyperglycemia-induced-the-alzheimer-s-proteins-and-promoted-loss-of-synaptic-proteins-in-advanced-age-female-goto-kakizaki-gk-rats
#2
Hiranya Pintana, Nattayaporn Apaijai, Sasiwan Kerdphoo, Wasana Pratchayasakul, Jirapas Sripetchwandee, Panan Suntornsaratoon, Narattaphol Charoenphandhu, Nipon Chattipakorn, Siriporn C Chattipakorn
Although both type 2 diabetes mellitus (T2DM) and aging are related with Alzheimer's disease (AD), the effects of aging on the Alzheimer's proteins and the synaptic markers in T2DM have not been investigated. This study, we hypothesized that T2DM rats with advanced-age, aggravates the reduction of synaptic proteins and an increase in the Alzheimer's protein markers. Goto-Kakizaki rats (GK) were used as a T2DM group and wild-type rats (WT) were used as a control group. Rats in each group were categorized by age into young-adult (7 months) and advanced-age rats (12...
June 23, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28650104/alzheimer-s-disease-and-metabolic-syndrome-a-link-from-oxidative-stress-and-inflammation-to-neurodegeneration
#3
REVIEW
Eduardo Rojas-Gutierrez, Guadalupe Muñoz-Arenas, Samuel Treviño, Blanca Espinosa, Raúl Chavez, Karla Rojas, Gonzalo Flores, Alfonso Díaz, Jorge Guevara
Alzheimer's disease (AD) is the most common cause of dementia and one of the most important causes of morbidity and mortality among the aging population. AD diagnosis is made post-mortem, and the two pathologic hallmarks, particularly evident in the end stages of the illness, are amyloid plaques and neurofibrillary tangles (NFT). Currently, there is no curative treatment for AD. Additionally, there is a strong relation between oxidative stress, metabolic syndrome (MetS) and AD. The high levels of circulating lipids and glucose imbalances amplify lipid peroxidation that gradually diminishes the antioxidant systems, causing high levels of oxidative metabolism that affects cell structure, leading to neuronal damage...
June 26, 2017: Synapse
https://www.readbyqxmd.com/read/28649604/combined-immunotherapy-with-anti-insulin-resistance-therapy-as-a-novel-therapeutic-strategy-against-neurodegenerative-diseases
#4
Yoshiki Takamatsu, Gilbert Ho, Wakako Koike, Shuei Sugama, Takato Takenouchi, Masaaki Waragai, Jianshe Wei, Kazunari Sekiyama, Makoto Hashimoto
Protein aggregation is a pathological hallmark of and may play a central role in the neurotoxicity in age-associated neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Accordingly, inhibiting aggregation of amyloidogenic proteins, including amyloid β and α-synuclein, has been a main therapeutic target for these disorders. Among various strategies, amyloid β immunotherapy has been extensively investigated in Alzheimer's disease, followed by similar studies of α-synuclein in Parkinson's disease...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/28646794/dexibuprofen-prevents-neurodegeneration-and-cognitive-decline-in-appswe-ps1de9-through-multiple-signaling-pathways
#5
Miren Ettcheto, Elena Sánchez-López, Laura Pons, Oriol Busquets, Jordi Olloquequi, Carlos Beas-Zarate, Merce Pallas, Maria Luisa García, Carme Auladell, Jaume Folch, Antoni Camins
The aim of the present study is to elucidate the neuronal pathways associated to NSAIDs causing a reduction of the risk and progression of Alzheimer's disease. The research was developed administering the active enantiomer of ibuprofen, dexibuprofen (DXI), in order to reduce associated gastric toxicity. DXI was administered from three to six-month-old female APPswe/PS1dE9 mice as a model of familial Alzheimer's disease. DXI treatment reduced the activation of glial cells and the cytokine release involved in the neurodegenerative process, especially TNFα...
June 15, 2017: Redox Biology
https://www.readbyqxmd.com/read/28635330/multiple-functions-of-insulin-degrading-enzyme-a-metabolic-crosslight
#6
Grazia R Tundo, Diego Sbardella, Chiara Ciaccio, Giuseppe Grasso, Magda Gioia, Andrea Coletta, Fabio Polticelli, Donato Di Pierro, Danilo Milardi, Peter Van Endert, Stefano Marini, Massimo Coletta
Insulin-degrading enzyme (IDE) is a ubiquitous zinc peptidase of the inverzincin family, which has been initially discovered as the enzyme responsible for insulin catabolism; therefore, its involvement in the onset of diabetes has been largely investigated. However, further studies on IDE unraveled its ability to degrade several other polypeptides, such as β-amyloid, amylin, and glucagon, envisaging the possible implication of IDE dys-regulation in the "aggregopathies" and, in particular, in neurodegenerative diseases...
June 21, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28626421/divergent-metabolic-regulation-of-autophagy-and-mtorc1-early-events-in-alzheimer-s-disease
#7
REVIEW
Mai A Shafei, Matthew Harris, Myra E Conway
Alzheimer's disease (AD) is a progressive disease associated with the production and deposition of amyloid β-peptide (Aβ) aggregates and neurofibrillary tangles, which lead to synaptic and neuronal damage. Reduced autophagic flux has been widely associated with the accumulation of autophagic vacuoles (AV), which has been proposed to contribute to aggregate build-up observed in AD. As such, targeting autophagy regulation has received wide review, where an understanding as to how this mechanism can be controlled will be important to neuronal health...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28622603/probing-supramolecular-protein-assembly-using-covalently-attached-fluorescent-molecular-rotors
#8
Markéta Kubánková, Ismael López-Duarte, James A Bull, Devkee M Vadukul, Louise C Serpell, Marie de Saint Victor, Eleanor Stride, Marina K Kuimova
Changes in microscopic viscosity and macromolecular crowding accompany the transition of proteins from their monomeric forms into highly organised fibrillar states. Previously, we have demonstrated that viscosity sensitive fluorophores termed 'molecular rotors', when freely mixed with monomers of interest, are able to report on changes in microrheology accompanying amyloid formation, and measured an increase in rigidity of approximately three orders of magnitude during aggregation of lysozyme and insulin. Here we extend this strategy by covalently attaching molecular rotors to several proteins capable of assembly into fibrils, namely lysozyme, fibrinogen and amyloid-β peptide (Aβ(1-42))...
September 2017: Biomaterials
https://www.readbyqxmd.com/read/28601647/metalloproteomic-and-differential-expression-in-plasma-in-a-rat-model-of-type-1-diabetes
#9
Camila Pereira Braga, José Cavalcante Souza Vieira, Aline de Lima Leite, Ana Angélica Henrique Fernandes, Marília Afonso Rabelo Buzalaf, Pedro de Magalhães Padilha
Type 1 diabetes is characterized by hyperglycemia, which in the chronic stage is associated with abnormalities in lipids, protein and, carbohydrate metabolism, as well as oxidative stress. New strategies for prevention and treatment are needed, as type 1 diabetes affects life quality and survival, and involves high-cost treatment. Proteomic and metalloproteomic studies can elucidate the functional and physiological aspects of biomolecules. In the present study, differential proteomics was used to identify potential biomarkers of diabetes in rat plasma associated with copper, selenium, zinc, and magnesium fractionation in control and diabetic rats, as well as diabetic rats treated with insulin...
June 8, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28598606/4s-hydroxylation-of-insulin-at-prob28-accelerates-hexamer-dissociation-and-delays-fibrillation
#10
Seth A Lieblich, Katharine Y Fang, Jackson K B Cahn, Jeffrey Rawson, Jeanne LeBon, H Teresa Ku, David A Tirrell
Daily injections of insulin provide lifesaving benefits to millions of diabetics. But currently available prandial insulins are suboptimal: The onset of action is delayed by slow dissociation of the insulin hexamer in the subcutaneous space, and insulin forms amyloid fibrils upon storage in solution. Here we show, through the use of noncanonical amino acid mutagenesis, that replacement of the proline residue at position 28 of the insulin B-chain (ProB28) by (4S)-hydroxyproline (Hzp) yields an active form of insulin that dissociates more rapidly, and fibrillates more slowly, than the wild-type protein...
June 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28595357/the-alzheimer-s-disease-transcriptome-mimics-the-neuroprotective-signature-of-igf-1-receptor-deficient-neurons
#11
Caroline George, Géraldine Gontier, Philippe Lacube, Jean-Christophe François, Martin Holzenberger, Saba Aïd
Seminal studies using post-mortem brains of patients with Alzheimer's disease evidenced aberrant insulin-like growth factor 1 receptor (IGF1R) signalling. Addressing causality, work in animal models recently demonstrated that long-term suppression of IGF1R signalling alleviates Alzheimer's disease progression and promotes neuroprotection. However, the underlying mechanisms remain largely elusive. Here, we showed that genetically ablating IGF1R in neurons of the ageing brain efficiently protects from neuroinflammation, anxiety and memory impairments induced by intracerebroventricular injection of amyloid-β oligomers...
June 8, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28590474/conducting-microhelices-from-self-assembly-of-protein-fibrils
#12
Fredrik G Bäcklund, Anders Elfwing, Chiara Musumeci, Fátima Ajjan, Viktoria Babenko, Wojciech Dzwolak, Niclas Solin, Olle Inganäs
Herein we utilize insulin to prepare amyloid based chiral helices with either right or left handed helicity. We demonstrate that the helices can be utilized as structural templates for the conducting polymer alkoxysulfonate poly(ethylenedioxythiophene) (PEDOT-S). The chirality of the helical assembly is transferred to PEDOT-S as demonstrated by polarized optical microscopy (POM) and Circular Dichroism (CD). Analysis of the helices by conductive atomic force microscopy (c-AFM) shows significant conductivity...
June 7, 2017: Soft Matter
https://www.readbyqxmd.com/read/28589443/metformin-a-future-therapy-for-neurodegenerative-diseases
#13
REVIEW
Magdalena Markowicz-Piasecka, Joanna Sikora, Aleksandra Szydłowska, Agata Skupień, Elżbieta Mikiciuk-Olasik, Kristiina M Huttunen
Type 2 diabetes mellitus (T2DM) is a complex, chronic and progressive metabolic disease, which is characterized by relative insulin deficiency, insulin resistance, and high glucose levels in blood. Esteemed published articles and epidemiological data exhibit an increased risk of developing Alzheimer's disease (AD) in diabetic pateints. Metformin is the most frequently used oral anti-diabetic drug, which apart from hypoglycaemic activity, improves serum lipid profiles, positively influences the process of haemostasis, and possesses anti-inflammatory properties...
June 6, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28582855/diabetes-and-alzheimer-s-disease-can-tea-phytochemicals-play-a-role-in-prevention
#14
Fernando W M A D Binosha, Geeshani Somaratne, Shehan Williams, Kathryn G Goozee, Harjinder Singh, Ralph N Martins
Dementia and diabetes mellitus are prevalent disorders in the elderly population. While recognized as two distinct diseases, diabetes has more recently recognized as a significant contributor to risk for developing dementia, and some studies make reference to type 3 diabetes, a condition resulting from insulin resistance in the brain. Alzheimer's disease, the most common form of dementia, and diabetes, interestingly, share underlying pathological processes, commonality in risk factors, and, importantly, pathways for intervention...
May 30, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28576073/zno-nanoflower-based-sensitive-nano-biosensor-for-amyloid-detection
#15
Najim Akhtar, Sanjay Kisan Metkar, Agnishwar Girigoswami, Koyeli Girigoswami
Zinc oxide (ZnO) is a semiconductor metal oxide nanoparticle with inherent optical properties. Among the different zinc oxide nanostructures, nanoflowers have greater surface area. Utilizing this property a reagentless biosensor has been developed for the detection of beta amyloids, a hallmark of neurodegenerative diseases like Alzheimer's disease, Creutzfeldt-Jakob Syndrome, insulin dependent type II diabetes etc. The poor fluorescence quantum yield and photobleaching effect of Thioflavin T (ThT) upon binding to the model insulin amyloid beta sheets in solution can be overcome by the present engineered biosensor where ThT acts as a target as well as a reporter to detect amyloids adsorbed on a solid template based on ZnO nanoflower...
September 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28574272/stimulus-responsive-supramolecular-aggregate-assembly-of-auramine-o-templated-by-sulfated-cyclodextrin
#16
Ankur A Awasthi, Prabhat K Singh
Self-aggregation of organic molecules is rarely seen with macrocyclic hosts like β-cyclodextrin, as they preferentially involve the formation of inclusion complexes with the guest molecule. In this contribution, we report the self-aggregation of a guest molecule induced by negatively charged sulfated β-cyclodextrin (SCD) to yield highly emissive aggregates of a recently projected amyloid marker dye, Auramine O (AuO). The SCD templated AuO aggregates display very different photophysics when compared to its reported behavior in a wide range of various chemical and biological environment but show a remarkable similarity with the recently reported photophysical behavior of AuO in human insulin fibrillar media, thus providing important insights into the molecular form of AuO responsible for its amyloid sensing ability...
June 19, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28569090/insulin-differentially-affects-the-distribution-kinetics-of-amyloid-beta-40-and-42-in-plasma-and-brain
#17
Suresh Kumar Swaminathan, Kristen M Ahlschwede, Vidur Sarma, Geoffry L Curran, Rajesh S Omtri, Teresa Decklever, Val J Lowe, Joseph F Poduslo, Karunya K Kandimalla
Impaired brain clearance of amyloid-beta peptides (Aβ) 40 and 42 across the blood-brain barrier (BBB) is believed to be one of the pathways responsible for Alzheimer's disease (AD) pathogenesis. Hyperinsulinemia prevalent in type II diabetes was shown to damage cerebral vasculature and increase Aβ accumulation in AD brain. However, there is no clarity on how aberrations in peripheral insulin levels affect Aβ accumulation in the brain. This study describes, for the first time, an intricate relation between plasma insulin and Aβ transport at the BBB...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28553678/population-study-confirms-serum-proteins-change-and-reveals-diagnostic-values-in-congenital-ventricular-septal-defect
#18
Jinghua Long, Shun Liu, Xiaoyun Zeng, Xiaoyun Yang, Hui Huang, Yongbo Zhang, Jiehua Chen, Yang Xu, Dongping Huang, Xiaoqiang Qiu
This study was designed to validate thrombospondin 1 (TSP-1), vascular endothelial-cadherin complex (VE-cad), insulin-like growth factor 2 (IGF-2), and amyloid precursor protein (APP) and assess their diagnostic value in ventricular septal defect (VSD). We investigated the serum levels of TSP-1, VE-cad, IGF-2, and APP by enzyme-linked immunosorbent assay in a hospital-based case-control study that included 40 VSD children and 40 healthy controls. Logistic regression analysis was applied to evaluate the relationship of the proteins and VSD, and receiver operating characteristic (ROC) curve was used to assess the diagnostic value of the significant proteins...
May 29, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28553348/neuroprotective-mechanism-of-kai-xin-san-upregulation-of-hippocampal-insulin-degrading-enzyme-protein-expression-and-acceleration-of-amyloid-beta-degradation
#19
Na Wang, Yong-Ming Jia, Bo Zhang, Di Xue, Maharjan Reeju, Yan Li, Shu-Ming Huang, Xue-Wei Liu
Kai Xin San is a Chinese herbal formula composed of Radix Ginseng, Poria, Radix Polygalae and Acorus Tatarinowii Rhizome. It has been used in China for many years for treating amnesia. Kai Xin San ameliorates amyloid-β (Aβ)-induced cognitive dysfunction and is neuroprotective in vivo, but its precise mechanism remains unclear. Expression of insulin-degrading enzyme (IDE), which degrades Aβ, is strongly correlated with cognitive function. Here, we injected rats with exogenous Aβ42 (200 μM, 5 μL) into the hippocampus and subsequently administered Kai Xin San (0...
April 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28551028/bidirectional-interactions-between-diabetes-and-alzheimer-s-disease
#20
REVIEW
Mitsuru Shinohara, Naoyuki Sato
Clinical studies have indicated that diabetes is associated with Alzheimer's disease (AD) and neurodegeneration. However, the mechanisms underlying this association have not been fully elucidated. Diabetes causes neurodegeneration by inducing changes in vascular function and structure, glucose metabolism, and insulin signaling, as well as by modifying β-amyloid (Aβ)/tau metabolisms. In turn, AD influences systemic glucose metabolism by inducing behavioral changes, memory disturbances, hypothalamic dysfunction, frailty and possibly plasma/peripheral Aβ level changes...
May 24, 2017: Neurochemistry International
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