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Insulin AND amyloid

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https://www.readbyqxmd.com/read/28229638/intranasal-insulin-treatment-improves-memory-and-learning-in-a-rat-amyloid-beta-model-of-alzheimer-s-disease
#1
S Farzampour, A Majdi, S Sadigh-Eteghad
Recently, insulin has been used as a pro-cognitive agent for the potential treatment of Alzheimer's disease (AD), because of its ability to cross the brain-blood barrier (BBB) by a saturable transport system. This study has been designed to evaluate the effects of intranasal insulin regimen, as a bypass system of BBB, on spatial memory in amyloid-beta (Aβ) model of AD in rat. Unilateral infusion of Aβ25-35 (10 nmol/2 µl/rat) into the lateral ventricular region of brain was used to produce a rat model of AD...
September 2016: Physiol Int
https://www.readbyqxmd.com/read/28228553/the-novel-mitochondrial-matrix-protease-ste23-is-required-for-efficient-presequence-degradation-and-processing
#2
Asli Aras Taskin, Cansu Kücükköse, Nils Burger, Dirk Mossmann, Chris Meisinger, F-Nora Vögtle
Around 70% of mitochondrial precursor proteins are imported from the cytosol via N-terminal presequences, which are cleaved upon exposure to the mitochondrial processing protease MPP in the matrix. Cleaved presequence peptides then need to be efficiently degraded and impairment of this clearance step e.g. by amyloid beta peptides causes a feedback inhibition of MPP leading ultimately to accumulation of immature precursor proteins within mitochondria. Degradation of mitochondrial peptides is performed by Cym1 in yeast and its homolog PreP in humans...
February 22, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28219449/ex-vivo-18-o-labeling-mass-spectrometry-identifies-a-peripheral-amyloid-%C3%AE-clearance-pathway
#3
Erik Portelius, Niklas Mattsson, Josef Pannee, Henrik Zetterberg, Magnus Gisslén, Hugo Vanderstichele, Eleni Gkanatsiou, Gabriela A N Crespi, Michael W Parker, Luke A Miles, Johan Gobom, Kaj Blennow
BACKGROUND: Proteolytic degradation of amyloid β (Aβ) peptides has been intensely studied due to the central role of Aβ in Alzheimer's disease (AD) pathogenesis. While several enzymes have been shown to degrade Aβ peptides, the main pathway of Aβ degradation in vivo is unknown. Cerebrospinal fluid (CSF) Aβ42 is reduced in AD, reflecting aggregation and deposition in the brain, but low CSF Aβ42 is, for unknown reasons, also found in some inflammatory brain disorders such as bacterial meningitis...
February 20, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28217771/detection-inhibition-and-disintegration-of-amyloid-fibrils-the-role-of-optical-probes-and-macrocyclic-receptors
#4
Achikanath C Bhasikuttan, Jyotirmayee Mohanty
Amyloid fibrils are formed by the aberrant aggregation of proteins into highly ordered β-sheet structures and are believed to be the root cause of several neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Prion diseases, etc. and have been the subject of extensive biochemical, biophysical and clinical studies. Developing methods for the early detection of fibril formation using optical spectroscopic techniques and inhibition/disintegration of amyloid fibrils/plaques by introducing small molecules have been a major challenge to establish a clinically facile therapeutic intervention to combat these neurodegenerative diseases...
February 20, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28198575/tat-biliverdin-reductase-a-protects-ins-1-cells-from-human-islet-amyloid-polypeptide-induced-cytotoxicity-by-alleviating-oxidative-stress-and-er-stress
#5
Su Jin Lee, Hyung Kyung Kang, Won Sik Eum, Jinseu Park, Soo Young Choi, Hyeok Yil Kwon
Human islet amyloid polypeptide (hIAPP), a major constituent of islet amyloid deposits, induces pancreatic β-cell apoptosis and eventually contributes to β-cell deficit in patients with type 2 diabetes mellitus (T2DM). In this study, Tat-mediated transduction of biliverdin reductase A (BLVRA) was investigated in INS-1 cells to examine whether exogenous supplementation of BLVRA prevented hIAPP-induced apoptosis and dysfunction in insulin secretion in β-cells. Tat-BLVRA fusion protein was efficiently delivered into INS-1 cells in a time- and dose-dependent manner...
February 15, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28188358/protective-effect-of-valproic-acid-in-streptozotocin-induced-sporadic-alzheimer-s-disease-mouse-model-possible-involvement-of-the-cholinergic-system
#6
Mirna Ezzat Sorial, Nesrine Salah El Dine El Sayed
Sporadic Alzheimer's disease (SAD) is a slowly progressive neurological disorder that is the most common form of dementia. Cholinergic system dysfunction and amyloid beta formation are the two main underlying pathological mechanisms for the disease development. In recent studies, insulin receptor desensitization and disturbances in the downstream effects of insulin receptor signaling were observed in the brains of Alzheimer's patients. Currently, intracereberoventricular (ICV) injection of streptozotocin (STZ) is found to induce behavioral, neurochemical, and structural alterations in animals resembling those found in SAD patients...
February 10, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28177017/surface-shear-viscosity-as-a-macroscopic-probe-of-amyloid-fibril-formation-at-a-fluid-interface
#7
Vignesh S Balaraj, Philip C H Zeng, Sean P Sanford, Samantha A McBride, Aditya Raghunandan, Juan M Lopez, Amir H Hirsa
Amyloidogenesis of proteins is of wide interest because amyloid structures are associated with many diseases, including Alzheimer's and type II diabetes. Dozens of different proteins of various sizes are known to form amyloid fibrils. While there are numerous studies on the fibrillization of insulin induced by various perturbations, shearing at fluid interfaces has not received as much attention. Here, we present a study of human insulin fibrillization at room temperature using a deep-channel surface viscometer...
February 8, 2017: Soft Matter
https://www.readbyqxmd.com/read/28159831/prion-like-protein-aggregates-and-type-2-diabetes
#8
Abhisek Mukherjee, Claudio Soto
Type 2 diabetes (T2D) is a highly prevalent metabolic disease characterized by chronic insulin resistance and β-cell dysfunction and loss, leading to impaired insulin release and hyperglycemia. Although the mechanism responsible for β-cell dysfunction and death is not completely understood, recent findings suggest that the accumulation of misfolded aggregates of the islet amyloid polypeptide (IAPP) in the islets of Langerhans may play an important role in pancreatic damage. Misfolding and aggregation of diverse proteins and their accumulation as amyloid in different organs is the hallmark feature in a group of chronic, degenerative diseases termed protein misfolding disorders (PMDs)...
February 3, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28145454/eugenol-prevents-amyloid-formation-of-proteins-and-inhibits-amyloid-induced-hemolysis
#9
Kriti Dubey, Bibin G Anand, Dolat Singh Shekhawat, Karunakar Kar
Eugenol has attracted considerable attention because of its potential for many pharmaceutical applications including anti-inflammatory, anti-tumorigenic and anti-oxidant properties. Here, we have investigated the effect of eugenol on amyloid formation of selected globular proteins. We find that both spontaneous and seed-induced aggregation processes of insulin and serum albumin (BSA) are significantly suppressed in the presence of eugenol. Isothermal titration calorimetric data predict a single binding site for eugenol-insulin complex confirming the affinity of eugenol for native soluble insulin species...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28137222/machine-learning-and-molecular-dynamics-based-insights-into-mode-of-actions-of-insulin-degrading-enzyme-modulators
#10
Salma Jamal, Sukriti Goyal, Asheesh Shanker, Abhinav Grover
BACKGROUND: Alzheimer's disease (AD) is one of the most common lethal neurodegenerative disorders having impact on the lives of millions of people worldwide. The disease lacks effective treatment options and the unavailability of the drugs to cure the disease necessitates the development of effectual anti-Alzheimer drugs. Several mechanisms have been reported underlying the association of the two disorders, diabetes and dementia, one among which is the insulin-degrading enzyme (IDE) which is known to degrade insulin as well beta-amyloid peptides...
January 30, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28124586/high-glucose-enhances-neurotoxicity-and-inflammatory-cytokine-secretion-by-stimulated-human-astrocytes
#11
Manpreet Bahniwal, Jonathan P Little, Andis Klegeris
BACKGROUND: Chronic neuroinflammation caused by activation of microglia and astrocytes in the brain contributes to neuronal loss and disease progression in Alzheimer's disease (AD). Recent research has identified type 2 diabetes mellitus (T2DM) as a risk factor for AD. High blood glucose (hyperglycemia) and the phenomenon of insulin resistance are being considered as the major factors contributing to an increased risk of AD. However, the mechanisms involved in this interaction remain unclear...
January 16, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28123476/the-expression-of-insulin-like-growth-factor-1-in-senior-patients-with-diabetes-and-dementia
#12
Yan-Ling Zhou, Shu-Qing Liu, Bin Yuan, Ning Lu
This study was conducted to investigate the expression of insulin-like growth factor-1 (IGF-1) in elderly patients with diabetes and dementia and to analyze the expression mechanism. A total of 30 senior patients with diabetes and dementia (group A), 30 senior patients with dementia but no diabetes (group B), 30 senior patients with diabetes but no dementia (group C), and 30 healthy seniors (group D) were continuously selected. The ELISA method was used to test the level of serum IGF-1, β-amyloid peptide (Aβ) and the phosphorylation of immunohistochemical staining of microtubule associated protein (tau protein)...
January 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28103595/identification-of-small-peptides-in-human-cerebrospinal-fluid-upon-amyloid-%C3%AE-degradation
#13
Naoki Mizuta, Kanta Yanagida, Takashi Kodama, Takeshi Tomonaga, Mako Takami, Hiroshi Oyama, Takashi Kudo, Manabu Ikeda, Masatoshi Takeda, Shinji Tagami, Masayasu Okochi
BACKGROUND: Amyloid-β (Aβ) degradation in brains of Alzheimer disease patients is a crucial focus for the clarification of disease pathogenesis. Nevertheless, the mechanisms underlying Aβ degradation in the human brain remain unclear. OBJECTIVE: This study aimed to quantify the levels of small C-terminal Aβ fragments generated upon Aβ degradation in human cerebrospinal fluid (CSF). METHODS: A fraction containing small peptides was isolated and purified from human CSF by high-pressure liquid chromatography...
2017: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/28103298/perinatal-choline-supplementation-reduces-amyloidosis-and-increases-choline-acetyltransferase-expression-in-the-hippocampus-of-the-appsweps1de9-alzheimer-s-disease-model-mice
#14
Tiffany J Mellott, Olivia M Huleatt, Bethany N Shade, Sarah M Pender, Yi B Liu, Barbara E Slack, Jan K Blusztajn
Prevention of Alzheimer's disease (AD) is a major goal of biomedical sciences. In previous studies we showed that high intake of the essential nutrient, choline, during gestation prevented age-related memory decline in a rat model. In this study we investigated the effects of a similar treatment on AD-related phenotypes in a mouse model of AD. We crossed wild type (WT) female mice with hemizygous APPswe/PS1dE9 (APP.PS1) AD model male mice and maintained the pregnant and lactating dams on a control AIN76A diet containing 1...
2017: PloS One
https://www.readbyqxmd.com/read/28094952/effect-of-an-enhanced-nose-to-brain-delivery-of-insulin-on-mild-and-progressive-memory-loss-in-the-senescence-accelerated-mouse
#15
Noriyasu Kamei, Misa Tanaka, Hayoung Choi, Nobuyuki Okada, Takamasa Ikeda, Rei Itokazu, Mariko Takeda-Morishita
Insulin is now considered to be a new drug candidate for treating dementias, such as Alzheimer's disease, whose pathologies are linked to insulin resistance in the brain. Our recent work has clarified that a noncovalent strategy involving cell-penetrating peptides (CPPs) can increase the direct transport of insulin from the nasal cavity into the brain parenchyma. The present study aimed to determine whether the brain insulin level increased by intranasal coadministration of insulin with the CPP penetratin has potential for treating dementia...
January 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28093241/new-isatin-derivative-inhibits-neurodegeneration-by-restoring-insulin-signaling-in-brain
#16
Meha Fatima Aftab, Shabbir Khan Afridi, Uzma Rasool Mughal, Aneela Karim, Darakhshan Jabeen Haleem, Nurul Kabir, Khalid M Khan, Rahman M Hafizur, Rizwana S Waraich
Diabetes is associated with neurodegeneration. Glycation ensues in diabetes and glycated proteins cause insulin resistance in brain resulting in amyloid plaques and NFTs. Also glycation enhances gliosis by promoting neuroinflammation. Currently there is no therapy available to target neurodegenration in brain therefore, development of new therapy that offers neuroprotection is critical. The objective of this study was to evaluate mechanistic effect of isatin derivative URM-II-81, an anti-glycation agent for improvement of insulin action in brain and inhibition of neurodegenration...
January 16, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28078611/hyperbaric-oxygen-prevents-cognitive-impairments-in-mice-induced-by-d-galactose-by-improving-cholinergic-and-anti-apoptotic-functions
#17
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
#18
Adam A Profit, Jayson Vedad, Ruel Z B Desamero
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 β-cells. Recent findings suggest that soluble hIAPP oligomers are the cytotoxic species responsible for β-cell loss whereas amyloid fibrils themselves may indeed be innocuous...
January 27, 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
#19
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
#20
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
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