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Alzheimers and obesity

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https://www.readbyqxmd.com/read/28071980/metabolic-syndrome-hypertension-and-nervous-system-injury-epidemiological-correlates
#1
Giovanna Ricci, Isabel Pirillo, Daniele Tomassoni, Ascanio Sirignano, Iolanda Grappasonni
: Metabolic syndrome (MetS) is a common and complex disorder combining hypertension, obesity, dyslipidemia, and insulin resistance. MetS represents a risk factor for changes in cognitive functions in older age, and several studies have suggested that MetS may be linked to dementia. This article reviews the main evidences about the relationship between MetS and neurodegenerative disease. Starting from an epidemiological point of view, the article analyzes medico-social aspects related to MetS, considering the reduction of work capacity and the condition of disability that it involves...
January 10, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/27988430/kinin-receptors-key-regulators-of-autoimmunity
#2
REVIEW
Rafael Cypriano Dutra
The central function of the immune system is to protect the host from environmental agents such as microbes or chemicals, thereby preserving the integrity of the body, and preventing the onset of illness and infection. Moreover, the immune system is constantly challenged to discriminate self vs. non-self and mediate the correct response, a phenomenon called self-tolerance. The failure of mechanisms responsible for self-tolerance and induction of an immune response against components of the self, induces autoimmunity and culminates however, in several autoimmune diseases...
December 15, 2016: Autoimmunity Reviews
https://www.readbyqxmd.com/read/27939359/a-story-of-metformin-butyrate-synergism-to-control-various-pathological-conditions-as-a-consequence-of-gut-microbiome-modification-genesis-of-a-wonder-drug
#3
REVIEW
Kunal Maniar, Amal Moideen, Ankur Mittal, Amol Patil, Amitava Chakrabarti, Dibyajyoti Banerjee
The most widely prescribed oral anti-diabetic agent today in the world today is a member of the biguanide class of drugs called metformin. Apart from its use in diabetes, it is currently being investigated for its potential use in many diseases such as cancer, cardiovascular diseases, Alzheimer's disease, obesity, comorbidities of diabetes such as retinopathy, nephropathy to name a few. Numerous in-vitro and in-vivo studies as well as clinical trials have been and are being conducted with a vast amount of literature being published every day...
December 8, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27933671/causal-inference-in-obesity-research
#4
REVIEW
P W Franks, N Atabaki-Pasdar
Obesity is a risk factor for a plethora of severe morbidities and premature death. Most supporting evidence comes from observational studies that are prone to chance, bias and confounding. Even data on the protective effects of weight loss from randomized controlled trials will be susceptible to confounding and bias if treatment assignment cannot be masked, which is usually the case with lifestyle and surgical interventions. Thus, whilst obesity is widely considered the major modifiable risk factor for many chronic diseases, its causes and consequences are often difficult to determine...
December 8, 2016: Journal of Internal Medicine
https://www.readbyqxmd.com/read/27932945/monoaminergic-and-histaminergic-strategies-and-treatments-in-brain-diseases
#5
REVIEW
Giuseppe Di Giovanni, Dubravka Svob Strac, Montse Sole, Mercedes Unzeta, Keith F Tipton, Dorotea Mück-Šeler, Irene Bolea, Laura Della Corte, Matea Nikolac Perkovic, Nela Pivac, Ilse J Smolders, Anna Stasiak, Wieslawa A Fogel, Philippe De Deurwaerdère
The monoaminergic systems are the target of several drugs for the treatment of mood, motor and cognitive disorders as well as neurological conditions. In most cases, advances have occurred through serendipity, except for Parkinson's disease where the pathophysiology led almost immediately to the introduction of dopamine restoring agents. Extensive neuropharmacological studies first showed that the primary target of antipsychotics, antidepressants, and anxiolytic drugs were specific components of the monoaminergic systems...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27923524/the-therapeutic-potential-of-metabolic-hormones-in-the-treatment-of-age-related-cognitive-decline-and-alzheimer-s-disease
#6
REVIEW
John Grizzanti, Hyoung-Gon Lee, Antoni Camins, Merce Pallas, Gemma Casadesus
Aging leads to a number of physiological alterations, specifically changes in circulating hormone levels, increases in fat deposition, decreases in metabolism, changes in inflammatory responses, and reductions in growth factors. These progressive changes in physiology and metabolism are exacerbated by modern culture and Western diet and give rise to diseases such as obesity, metabolic syndrome, and type 2 (non-insulin-dependent) diabetes (T2D). These age and lifestyle-related metabolic diseases are often accompanied by insulin and leptin resistance, as well as aberrant amylin production and signaling...
December 2016: Nutrition Research
https://www.readbyqxmd.com/read/27920671/proceedings-of-the-fourth-annual-deep-brain-stimulation-think-tank-a-review-of-emerging-issues-and-technologies
#7
Wissam Deeb, James J Giordano, Peter J Rossi, Alon Y Mogilner, Aysegul Gunduz, Jack W Judy, Bryan T Klassen, Christopher R Butson, Craig Van Horne, Damiaan Deny, Darin D Dougherty, David Rowell, Greg A Gerhardt, Gwenn S Smith, Francisco A Ponce, Harrison C Walker, Helen M Bronte-Stewart, Helen S Mayberg, Howard J Chizeck, Jean-Philippe Langevin, Jens Volkmann, Jill L Ostrem, Jonathan B Shute, Joohi Jimenez-Shahed, Kelly D Foote, Aparna Wagle Shukla, Marvin A Rossi, Michael Oh, Michael Pourfar, Paul B Rosenberg, Peter A Silburn, Coralie de Hemptine, Philip A Starr, Timothy Denison, Umer Akbar, Warren M Grill, Michael S Okun
This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome...
2016: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/27911319/autotaxin-is-related-to-metabolic-dysfunction-and-predicts-alzheimer-s-disease-outcomes
#8
Kelsey E McLimans, Auriel A Willette
BACKGROUND: Obesity and insulin resistance are associated with neuropathology and cognitive decline in Alzheimer's disease (AD). OBJECTIVE: Ecto-nucleotide pyrophosphatase/phosphodiesterase 2, also called autotaxin, is produced by beige adipose tissue, regulates metabolism, and is higher in AD prefrontal cortex (PFC). Autotaxin may be a novel biomarker of dysmetabolism and AD. METHODS: We studied Alzheimer's Disease Neuroimaging Initiative participants who were cognitively normal (CN; n = 86) or had mild cognitive impairment (MCI; n = 135) or AD (n = 66)...
December 1, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27863851/long-term-exposition-to-a-high-fat-diet-favors-the-appearance-of-%C3%AE-amyloid-depositions-in-the-brain-of-c57bl-6j-mice-a-potential-model-of-sporadic-alzheimer-s-disease
#9
Oriol Busquets, Miren Ettcheto, Mercè Pallàs, Carlos Beas-Zarate, Ester Verdaguer, Carme Auladell, Jaume Folch, Antoni Camins
AIMS: The sporadic and late-onset form of Alzheimer's disease (AD) constitutes the most common form of dementia. This non-familiar form could be a consequence of metabolic syndrome, characterized by obesity and the development of a brain-specific insulin resistance known as type III diabetes. This work demonstrates the development of a significant AD-like neuropathology due to these metabolic alterations. METHODS: C57BL/6J mice strain were divided into two groups, one fed with a diet rich in palmitic acid (high-fat diet, HFD) since their weaning until 16 months of age, and another group used as a control with a regular diet...
November 15, 2016: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/27846718/-rab-proteins-intracellular-transport-and-cancer
#10
R Černochová, M Nekulová, J Holčaková
BACKGROUND: Rab proteins are small monomeric enzymes which belong to the large Ras protein superfamily and allow hydrolysis of guanosine triphosphate (GTP) to guanosine (GDP). Up to now more than 60 proteins have been described that act primarily as regulators of intracellular transport. Rab GTPases are mostly located at the intracellular membranes, where they provide connections to motor proteins and to the cytoskeleton and control various steps of the traffic pathways including the formation and movement of vesicles or membrane fusion controlling secretion, endocytosis, recycling and degradation of proteins...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27832290/sorting-receptor-sorla-cellular-mechanisms-and-implications-for-disease
#11
REVIEW
Vanessa Schmidt, Aygul Subkhangulova, Thomas E Willnow
Sorting-related receptor with A-type repeats (SORLA) is an intracellular sorting receptor that directs cargo proteins, such as kinases, phosphatases, and signaling receptors, to their correct location within the cell. The activity of SORLA assures proper function of cells and tissues, and receptor dysfunction is the underlying cause of common human malignancies, including Alzheimer's disease, atherosclerosis, and obesity. Here, we discuss the molecular mechanisms that govern sorting of SORLA and its cargo in multiple cell types, and why genetic defects in this receptor results in devastating diseases...
November 10, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27815120/identification-of-lead-small-molecule-inhibitors-of-glycogen-synthase-kinase-3-beta-using-a-fragment-linking-strategy
#12
Jinhee Kim, Yonghoon Moon, Sungwoo Hong
Glycogen synthase kinase-3 beta (GSK3β) kinase serves as a promising therapeutic target for the treatment of various human diseases, such as diabetes, obesity, and Alzheimer's disease. In this study, we report lead GSK3β inhibitors identified using a fragment-linking strategy. Through the systematic exploration, a six-atom chain unit bearing the rigid double bond was found to be a suitable linker connecting two fragments, which enables favorable contacts with backbone groups of residues in the pockets. As a consequence, potent GSK3β inhibitor 9i was found with IC50 values of 19nM...
October 22, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27802235/mitochondrial-abnormalities-and-synaptic-loss-underlie-memory-deficits-seen-in-mouse-models-of-obesity-and-alzheimer-s-disease
#13
Isaura V A Martins, Jack Rivers-Auty, Stuart M Allan, Catherine B Lawrence
Obesity is associated with impaired memory in humans, and obesity induced by high-fat diets leads to cognitive deficits in rodents and in mouse models of Alzheimer's disease (AD). However, it remains unclear how high-fat diets contribute to memory impairment. Therefore, we tested the effect of a high-fat diet on memory in male and female control non-transgenic (Non-Tg) and triple-transgenic AD (3xTgAD) mice and determined if a high-fat diet caused similar ultrastructural abnormalities to those observed in AD...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27796748/relationship-between-obesity-alzheimer-s-disease-and-parkinson-s-disease-an-astrocentric-view
#14
REVIEW
Cynthia Alexandra Martin-Jiménez, Diana Milena Gaitán-Vaca, Valentina Echeverria, Janneth González, George E Barreto
Obesity is considered one of the greatest risk to human health and is associated with several factors including genetic components, diet, and physical inactivity. Recently, the relationship between obesity and numerous progressive and aging-related neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD) have been observed. Thus, the involvement of the most abundant and heterogeneous group of glial cells in neurodegenerative diseases, the astrocytes, is caused by a combination of the failure on their normal homeostatic functions and the increase of toxic metabolites upon pathological event...
October 28, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27793638/tau-hyperphosphorylation-in-the-brain-of-ob-ob-mice-is-due-to-hypothermia-importance-of-thermoregulation-in-linking-diabetes-and-alzheimer-s-disease
#15
Maud Gratuze, Noura B El Khoury, Andréanne Turgeon, Carl Julien, François Marcouiller, Françoise Morin, Robert A Whittington, André Marette, Frédéric Calon, Emmanuel Planel
Over the last few decades, there has been a significant increase in epidemiological studies suggesting that type 2 diabetes (T2DM) is linked to a higher risk of Alzheimer's disease (AD). However, how T2DM affects AD pathology, such as tau hyperphosphorylation, is not well understood. In this study, we investigated the impact of T2DM on tau phosphorylation in ob/ob mice, a spontaneous genetic model of T2DM. Tau phosphorylation at the AT8 epitope was slightly elevated in 4-week-old ob/ob mice while 26-week-old ob/ob mice exhibited tau hyperphosphorylation at multiple tau phospho-epitopes (Tau1, CP13, AT8, AT180, PHF1)...
February 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/27789118/adverse-structural-and-functional-effects-of-marijuana-on-the-brain-evidence-reviewed
#16
REVIEW
David E Mandelbaum, Suzanne M de la Monte
The growing use and legalization of cannabis are leading to increased exposures across all age groups, including in adolescence. The touting of its medicinal values stems from anecdotal reports related to treatment of a broad range of illnesses including epilepsy, multiple sclerosis, muscle spasms, arthritis, obesity, cancer, Alzheimer disease, Parkinson disease, post-traumatic stress, inflammatory bowel disease, and anxiety. However, anecdotal data and the high level of interest in this treatment must not obscure objective assessments of any potential and realized short- and long-term adverse effects of cannabis, particularly with respect to age of onset and chronicity of exposure...
January 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/27773783/chitosan-oligosaccharide-biological-activities-and-potential-therapeutic-applications
#17
REVIEW
Chatchai Muanprasat, Varanuj Chatsudthipong
Chitosan oligosaccharide (COS) is an oligomer of β-(1➔4)-linked d-glucosamine. COS can be prepared from the deacetylation and hydrolysis of chitin, which is commonly found in the exoskeletons of arthropods and insects and the cell walls of fungi. COS is water soluble, non-cytotoxic, readily absorbed through the intestine and mainly excreted in the urine. Of particular importance, COS and its derivatives have been demonstrated to possess several biological activities including anti-inflammation, immunostimulation, anti-tumor, anti-obesity, anti-hypertension, anti-Alzheimer's disease, tissue regeneration promotion, drug and DNA delivery enhancement, anti-microbial, anti-oxidation and calcium-absorption enhancement...
October 20, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27771511/high-fat-diet-induces-brain-insulin-resistance-and-cognitive-impairment-in-mice
#18
Vishal Kothari, Yuwen Luo, Talia Tornabene, Ann Marie O'Neill, Michael W Greene, Thangiah Geetha, Jeganathan Ramesh Babu
High fat diet-induced obesity is associated with insulin resistance (IR) and other chronic, diet related illnesses, including dementia. Alzheimer disease is the most common form of dementia, and is characterized by the presence of amyloid plaques and neurofibrillary tangles in brain. This study was designed to determine whether diet-induced changes in peripheral insulin sensitivity could contribute to alterations in brain insulin signaling and cognitive functions. Six week old, male C57BL/6NHsd mice were randomly assigned a high fat diet (40% energy from fat) with 42g/L liquid sugar (HFS) added to the drinking water or a normal chow diet (12% energy from fat) for 14weeks...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27754286/br-07-1-development-of-the-cell-microarray-for-high-throughput-analysis-of-gut-microbiota
#19
Seong-Tshool Hong
The human intestine contains a massive and complex microbial community called gut microbiota. A typical human carries 100 trillion microbes in his/her body which is 10 times greater than the number of their host cells, i.e. whole number of human cells. A combined microbial genome constituting gut microbiota is well excess our own human genome. The microbial composition of gut microbiotata and its role on diseases became a booming area of research, presenting a new paradigm of opportunities for modern medicines...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27748164/evaluation-of-human-microtubule-affinity-regulating-kinase-4-inhibitors-fluorescence-binding-studies-enzyme-and-cell-assays
#20
Farha Naz, Neha Sami, Abu Turab Naqvi, Asimul Islam, Faizan Ahmad, Md Imtaiyaz Hassan
Human microtubule affinity-regulating kinase 4 (MARK4) is considered as an encouraging drug target for the design and development of inhibitors to cure several life threatening diseases such as Alzheimer disease, cancer, obesity and type-II diabetes. Recently, we have reported four ligands namely, BX-912, BX-795, PKR-inhibitor and OTSSP167 (hydrochloride) which bind preferentially to the two different constructs of human MARK4 containing kinase domain. To ensure the role of ubiquitin associated (UBA) domain in the ligand binding, we made a newer construct of MARK4 which contain both kinase and UBA domains, named as MARK4-F3...
October 16, 2016: Journal of Biomolecular Structure & Dynamics
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