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Alzheimers and diabetes

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https://www.readbyqxmd.com/read/29782833/insights-into-stabilizing-forces-in-amyloid-fibrils-of-differing-sizes-from-polarizable-molecular-dynamics-simulations
#1
Darcy S Davidson, Anne M Brown, Justin A Lemkul
Pathological aggregation of amyloid-forming proteins is a hallmark of a number of human diseases, including Alzheimer's, type 2 diabetes, Parkinson's, and more. Despite having very different primary amino acid sequences, these amyloid proteins form similar supramolecular, fibril structures that are highly resilient to physical and chemical denaturation. To better understand the structural stability of disease-related amyloids and to gain a greater understanding of factors that stabilize functional amyloid assemblies, insights into tertiary and quaternary interactions are needed...
May 18, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29779477/exposure-of-aggregation-prone-segments-is-the-requirement-for-amyloid-fibril-formation
#2
Shreya Pramanik, Basir Ahmad
Arranging into well-organized fibrillar aggregate, commonly known as amyloid fibril is an inherent property of any polypeptide chain. Amyloid fibrils are associated with a number of severe human pathologies like the Alzheimer's disease, Parkinson's disease, type2 diabetes and many more. Recent studies suggest that most of the fibrils are inert and extremely stable, thus could be used for the bio-nanotechnological applications. As the native state is protected by evolution from aggregation under physiological condition, understanding the structure of aggregation precursor state (APS) will be of extreme importance to decode mechanism of its formation and prevention...
May 20, 2018: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/29777753/characterization-of-impaired-cerebrovascular-structure-in-app-ps1-mouse-brains
#3
Kee-Chan Ahn, Cameron R Learman, Gary L Dunbar, Panchanan Maiti, Won-Cheoul Jang, Hyeon-Cheol Cha, Mee-Sook Song
Alzheimer's disease (AD) is defined by senile plaques, tauopathy and neuronal cell death in specific area of the brain. Recent studies suggest that neurovascular dysfunction may be an integral part of AD pathogenesis, contributing to the onset and development of AD pathologies such as neuronal death, inflammatory response, and breakdown of blood brain barrier (BBB). In addition, vascular complications caused by age-related metabolic diseases such as diabetes and high blood pressure have high incidence in development of dementia and AD...
May 16, 2018: Neuroscience
https://www.readbyqxmd.com/read/29773016/is-cannabidiol-a-promising-substance-for-new-drug-development-a-review-of-its-potential-therapeutic-applications
#4
Nida Noreen, Faqir Muhammad, Bushra Akhtar, Farooq Azam, Muhammad Irfan Anwar
The pharmacological importance of cannabidiol (CBD) has been in study for several years. CBD is the major nonpsychoactive constituent of plant Cannabis sativa and its administration is associated with reduced side effects. Currently, CBD is undergoing a lot of research which suggests that it has no addictive effects, good safety profile and has exhibited powerful therapeutic potential in several vital areas. It has wide spectrum of action because it acts through endocannabinoid receptors; CB1 and CB2 and it also acts on other receptors, such as GPR18, GPR55, GPR 119, 5HT1A, and TRPV2...
2018: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/29760188/depression-in-type-1-diabetes-was-associated-with-high-levels-of-circulating-galectin-3
#5
Eva O Melin, Jonatan Dereke, Maria Thunander, Magnus Hillman
OBJECTIVE: Neuroinflammatory responses are implicated in depression. The aim was to explore whether depression in patients with type 1 diabetes (T1D) was associated with high circulating galectin-3, controlling for metabolic variables, s-creatinine, life style factors, medication, and cardiovascular complications. DESIGN: Cross-sectional. METHODS: Participants were T1D patients (n=283, 56% men, age 18-59 years, diabetes duration ≥1 year)...
May 14, 2018: Endocrine Connections
https://www.readbyqxmd.com/read/29758944/the-conundrum-of-gsk3-inhibitors-is-it-the-dawn-of-a-new-beginning
#6
Ratan V Bhat, Ulf Andersson, Shalini Andersson, Laurent Knerr, Udo Bauer, Anna Sundgren Andersson
Spanning over three decades of extensive drug discovery research, the efforts to develop a potent and selective GSK3 inhibitor as a therapeutic for the treatment of type 2 diabetes, Alzheimer's disease (AD), bipolar disorders and cancer have been futile. Since its initial discovery in 1980 and subsequent decades of research, one cannot underscore the importance of the target and the promise of a game changing disease modifier. Several pharmaceutical companies, biotech companies, and academic institutions raged in a quest to unravel the biology and discover potent and selective GSK3 inhibitors, some of which went through clinical trials...
May 11, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29757991/a-review-the-bioactivities-and-pharmacological-applications-of-polygonatum-sibiricum-polysaccharides
#7
REVIEW
Xiaowei Cui, Shiyuan Wang, Hui Cao, Hong Guo, Yujuan Li, Fangxue Xu, Mengmeng Zheng, Xiaozhi Xi, Chunchao Han
Traditional Chinese Medicine (TCM) has been widely used in China and is regarded as the most important therapeutic. Polygonatum sibiricum (PS), a natural plant used in traditional Chinese medicine, has various functions associated with a number of its components. There are many compositions in PS including polysaccharides, steroids, anthraquinone, alkaloids, cardiac glycosides, lignin, vitamins, various acids, and so on. Of these, polysaccharides play a significant role in PS-based therapeutics. This article summarizes Polygonatum sibiricum polysaccharides (PSP) have many pharmacological applications and biological activities, such as their antioxidant activity, anti-aging activity, an anti-fatigue effect, immunity enhancement effect, antibacterial effect, anti-inflammatory effect, hypolipidemic and antiatherosclerotic effects, anti-osteoporosis effect, liver protection, treatment of diabetes mellitus (DM), anti-cancer effect, and may help prevent Alzheimer's disease, and so on...
May 14, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29755410/mitochondrial-chaperones-in-the-brain-safeguarding-brain-health-and-metabolism
#8
José Pedro Castro, Kristina Wardelmann, Tilman Grune, André Kleinridders
The brain orchestrates organ function and regulates whole body metabolism by the concerted action of neurons and glia cells in the central nervous system. To do so, the brain has tremendously high energy consumption and relies mainly on glucose utilization and mitochondrial function in order to exert its function. As a consequence of high rate metabolism, mitochondria in the brain accumulate errors over time, such as mitochondrial DNA (mtDNA) mutations, reactive oxygen species, and misfolded and aggregated proteins...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29755365/the-relation-between-capillary-transit-times-and-hemoglobin-saturation-heterogeneity-part-1-theoretical-models
#9
Adrien Lücker, Timothy W Secomb, Bruno Weber, Patrick Jenny
Capillary dysfunction impairs oxygen supply to parenchymal cells and often occurs in Alzheimer's disease, diabetes and aging. Disturbed capillary flow patterns have been shown to limit the efficacy of oxygen extraction and can be quantified using capillary transit time heterogeneity (CTH). However, the transit time of red blood cells (RBCs) through the microvasculature is not a direct measure of their capacity for oxygen delivery. Here we examine the relation between CTH and capillary outflow saturation heterogeneity (COSH), which is the heterogeneity of blood oxygen content at the venous end of capillaries...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29748034/ampk-induced-memory-improvements-in-the-diabetic-population-a-case-study
#10
Alicia Halikas, Kelly J Gibas
Diabetics in mid-life carry a 1.5 times higher risk of developing Alzheimer's disease than those diagnosed with diabetes (T2D) later in life [1]. Recent research points to accelerated cognitive decline within a range of 20%-50% for middle-aged diabetics as compared to non-diabetic populations [2,3]. Metabolic syndrome (MetS), a type 2 diabetes (T2D) precursor, is also linked to MCI and AD pathologies via hypo-metabolic brain circuitry that inhibits glucose metabolism and attenuates cognitive function [4]. Dysregulation of intracellular and extracellular signaling as mediated by the mTOR and AMPK pathways is the result...
April 27, 2018: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/29744852/experimental-and-computational-protocols-for-studies-of-cross-seeding-amyloid-assemblies
#11
Baiping Ren, Rundong Hu, Mingzhen Zhang, Yonglan Liu, Lijian Xu, Binbo Jiang, Jie Ma, Buyong Ma, Ruth Nussinov, Jie Zheng
Alzheimer's disease (AD) and type 2 diabetes (T2D) are two common protein aggregation diseases. Compelling evidence has shown a link between AD and T2D, which may derive from interspecies cross-sequence interactions between amyloid-β peptide (Aβ), associated with AD, and human islet amyloid polypeptide (hIAPP), associated with T2D. Herein, we present experimental and computational protocols and tools to study the aggregate structures and kinetics, conformational conversion, and molecular interactions of Aβ-hIAPP mixtures...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29744830/replica-exchange-molecular-dynamics-a-practical-application-protocol-with-solutions-to-common-problems-and-a-peptide-aggregation-and-self-assembly-example
#12
Ruxi Qi, Guanghong Wei, Buyong Ma, Ruth Nussinov
Protein aggregation is associated with many human diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and type II diabetes (T2D). Understanding the molecular mechanism of protein aggregation is essential for therapy development. Molecular dynamics (MD) simulations have been shown as powerful tools to study protein aggregation. However, conventional MD simulations can hardly sample the whole conformational space of complex protein systems within acceptable simulation time as it can be easily trapped in local minimum-energy states...
2018: Methods in Molecular Biology
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
#13
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/29738850/intermittent-streptozotocin-administration-induces-behavioral-and-pathological-features-relevant-to-alzheimer-s-disease-and-vascular-dementia
#14
Andrew S Murtishaw, Chelcie F Heaney, Monica M Bolton, Krystal Courtney D Belmonte, Michael A Langhardt, Jefferson W Kinney
RATIONALE: Diabetes mellitus (DM) is a major risk factor for Alzheimer's disease and vascular dementia. Few animal models exist that focus on the metabolic contributions to dementia onset and progression. Thus, there is strong scientific rationale to explore the effects of streptozotocin (STZ), a diabetogenic compound, on vascular and inflammatory changes within the brain. OBJECTIVE AND METHODS: The present study was designed to evaluate the effect of staggered, low-dose administration of STZ on behavioral and cognitive deficits, neuroinflammation, tau pathology, and histopathological alterations related to dementia...
May 5, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29738349/a-pilot-study-of-pancreatic-islet-amyloid-pet-imaging-with-18f-fddnp
#15
Zhi Lu, Jinghui Xie, Ran Yan, Zilin Yu, Zhigang Sun, Fei Yu, Xiaoyan Gong, Hongbo Feng, Jing Lu, Yanjun Zhang
OBJECTIVES: Pancreatic islet amyloid deposition occurs before β-cell damage in type 2 diabetes mellitus patients. The islet and Alzheimer's disease β-amyloid shares similar secondary structures. The Alzheimer's disease β-amyloid targeting tracer [F]FDDNP could be used to image pancreatic islet amyloid with PET. PATIENTS AND METHODS: Consecutive pancreatic tissue sections from a 69-year-old male type 2 diabetes mellitus patient were stained by hematoxylin and eosin, anti-amylin antibody, Congo Red, periodic acid-Schiff, and [F]FDDNP reference compound, respectively...
May 5, 2018: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/29736736/the-medial-septum-is-insulin-resistant-in-the-ad-presymptomatic-phase-rescue-by-nerve-growth-factor-driven-irs-1-activation
#16
Valentina Sposato, Nadia Canu, Elena Fico, Salvatore Fusco, Giulia Bolasco, Maria Teresa Ciotti, Matteo Spinelli, Delio Mercanti, Claudio Grassi, Viviana Triaca, Pietro Calissano
Basal forebrain cholinergic neurons (BFCN) are key modulators of learning and memory and are high energy-demanding neurons. Impaired neuronal metabolism and reduced insulin signaling, known as insulin resistance, has been reported in the early phase of Alzheimer's disease (AD), which has been suggested to be "Type 3 Diabetes." We hypothesized that BFCN may develop insulin resistance and their consequent failure represents one of the earliest event in AD. We found that a condition reminiscent of insulin resistance occurs in the medial septum of 3 months old 3×Tg-AD mice, reported to develop typical AD histopathology and cognitive deficits in adulthood...
May 7, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29732634/berberine-pathways-to-protect-neurons
#17
REVIEW
Xiaorui Lin, Nan Zhang
Berberine, an isoquinoline alkaloid, is demonstrated to have a variety of pharmacologic effects. Widely used as nonprescription drug for diarrhea, berberine has also broadened its applications in therapies of cardiovascular diseases, diabetes mellitus, tumor, and so forth. However, researches about berberine's protective effects on nervous system are still so insufficient that clinical uses cannot popularize and underlying molecules mechanisms are confused and incomplete. Well-known pathways such as Pl3K/Akt/Bcl-2 pathway, Nrf2/HO-1 pathway, and MAPK signaling pathway help berberine to protect neurons through antiapoptotic, antioxidative, and anti-inflammatory activities...
May 6, 2018: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29729422/genetically-reducing-mtor-signaling-rescues-central-insulin-dysregulation-in-a-mouse-model-of-alzheimer-s-disease
#18
Antonella Caccamo, Ramona Belfiore, Salvatore Oddo
Alzheimer's disease (AD) is the most common neurodegenerative disease. The causes of sporadic AD, which represents more than 95% of AD cases, are unknown. Several AD risk factors have been identified and among these, type 2 diabetes increases the risk of developing AD by 2-fold. However, the mechanisms by which diabetes contributes to AD pathogenesis remain elusive. The mammalian target of rapamycin (mTOR) is a protein kinase that plays a crucial role in the insulin signaling pathway and has been linked to AD...
April 5, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29728772/implementing-a-mediterranean-style-diet-outside-the-mediterranean-region
#19
REVIEW
Karen J Murphy, Natalie Parletta
PURPOSE OF REVIEW: Populations surrounding the Mediterranean basin have traditionally reaped health benefits from a Mediterranean diet (MedDiet), which may benefit Westernized countries plagued by chronic disease. But is it feasible to implement beyond the Mediterranean? To answer this question, we present evidence from randomized controlled trials that achieved high dietary compliance rates with subsequent physical and mental health benefits. RECENT FINDINGS: In the 1960s, the Seven Countries Study identified dietary qualities of Mediterranean populations associated with healthy aging and longevity...
May 4, 2018: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/29720722/development-of-comorbidities-in-men-with-prostate-cancer-treated-with-androgen-deprivation-therapy-an-australian-population-based-cohort-study
#20
Huah Shin Ng, Bogda Koczwara, David Roder, Agnes Vitry
BACKGROUND: The increasing use of androgen deprivation therapy has prompted further evaluation of its potential adverse effects as the treatment may exacerbate or increase the risk of developing new comorbid diseases. This study aims to assess the patterns of comorbidities among Australian men with prostate cancer treated with androgen deprivation therapy. METHODS: Pharmaceutical Benefits Scheme (PBS) 10% data between 1 January 2003 and 31 December 2014 was utilised in this retrospective cohort study...
May 2, 2018: Prostate Cancer and Prostatic Diseases
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