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Alzheimers and obesity

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https://www.readbyqxmd.com/read/27920671/proceedings-of-the-fourth-annual-deep-brain-stimulation-think-tank-a-review-of-emerging-issues-and-technologies
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
October 11, 2016: 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
#8
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
#9
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)...
October 26, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27789118/adverse-structural-and-functional-effects-of-marijuana-on-the-brain-evidence-reviewed
#10
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, it is essential that anecdotal data and the high level of interest in this treatment 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...
September 13, 2016: Pediatric Neurology
https://www.readbyqxmd.com/read/27773783/chitosan-oligosaccharide-biological-activities-and-potential-therapeutic-applications
#11
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
#12
Vishal Kothari, Yuwen Luo, Talia Tornabene, Ann Marie O'Neill, Michael W Greene, Geetha Thangiah, 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. Four 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...
October 19, 2016: 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
#13
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
#14
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
https://www.readbyqxmd.com/read/27739227/insulin-signalling-in-alzheimer-s-disease-and-diabetes-from-epidemiology-to-molecular-links
#15
E M Ribe, S Lovestone
As populations across the world both age and become more obese, the numbers of individuals with Alzheimer's disease and diabetes are increasing; posing enormous challenges for society and consequently becoming priorities for governments and global organizations. These issues, an ageing population at risk of neurodegenerative diseases such as Alzheimer's disease and an increasingly obese population at risk of metabolic alterations such as type 2 diabetes, are usually considered as independent conditions, but increasing evidence from both epidemiological and molecular studies link these disorders...
October 14, 2016: Journal of Internal Medicine
https://www.readbyqxmd.com/read/27730513/middle-aged-diabetic-females-and-males-present-distinct-susceptibility-to-alzheimer-disease-like-pathology
#16
E Candeias, A I Duarte, I Sebastião, M A Fernandes, A I Plácido, C Carvalho, S Correia, R X Santos, R Seiça, M S Santos, C R Oliveira, P I Moreira
Type 2 diabetes (T2D) is a highly concerning public health problem of the twenty-first century. Currently, it is estimated that T2D affects 422 million people worldwide with a rapidly increasing prevalence. During the past two decades, T2D has been widely shown to have a major impact in the brain. This, together with the cognitive decline and increased risk for dementia upon T2D, may arise from the complex interaction between normal brain aging and central insulin signaling dysfunction. Among the several features shared between T2D and some neurodegenerative disorders (e...
October 11, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27725441/perturbed-calcineurin-nfat-signaling-is-associated-with-the-development-of-alzheimer-s-disease
#17
Masashi Asai, Aimi Kinjo, Shoko Kimura, Ryotaro Mori, Takashi Kawakubo, Keiro Shirotani, Sosuke Yagishita, Kei Maruyama, Nobuhisa Iwata
Down syndrome (DS), the most common genetic disorder, is caused by trisomy 21. DS is accompanied by heart defects, hearing and vision problems, obesity, leukemia, and other conditions, including Alzheimer's disease (AD). In comparison, most cancers are rare in people with DS. Overexpression of dual specificity tyrosine-phosphorylation-regulated kinase 1A and a regulator of calcineurin 1 located on chromosome 21 leads to excessive suppression of the calcineurin-nuclear factor of activated T cells (NFAT) signaling pathway, resulting in reduced expression of a critical angiogenic factor...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27722929/pesticides-an-update-of-human-exposure-and-toxicity
#18
Sara Mostafalou, Mohammad Abdollahi
Pesticides are a family of compounds which have brought many benefits to mankind in the agricultural, industrial, and health areas, but their toxicities in both humans and animals have always been a concern. Regardless of acute poisonings which are common for some classes of pesticides like organophosphoruses, the association of chronic and sub-lethal exposure to pesticides with a prevalence of some persistent diseases is going to be a phenomenon to which global attention has been attracted. In this review, incidence of various malignant, neurodegenerative, respiratory, reproductive, developmental, and metabolic diseases in relation to different routes of human exposure to pesticides such as occupational, environmental, residential, parental, maternal, and paternal has been systematically criticized in different categories of pesticide toxicities like carcinogenicity, neurotoxicity, pulmonotoxicity, reproductive toxicity, developmental toxicity, and metabolic toxicity...
October 8, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27688858/is-it-possible-to-delay-or-prevent-age-related-cognitive-decline
#19
REVIEW
Jean-Pierre Michel
Already in the 90s, Khachaturian stated that postponing dementia onset by five years would decrease the prevalence of the late onset dementia by 50%. After two decades of lack of success in dementia drug discovery and development, and knowing that worldwide, currently 36 million patients have been diagnosed with Alzheimer's disease, a number that will double by 2030 and triple by 2050, the World Health Organization and the Alzheimer's Disease International declared that prevention of cognitive decline was a 'public health priority...
September 2016: Korean Journal of Family Medicine
https://www.readbyqxmd.com/read/27671821/celastrol-and-its-role-in-controlling%C3%A2-chronic-diseases
#20
Shivaprasad H Venkatesha, Kamal D Moudgil
Celastrol, a triterpenoid derived from traditional Chinese medicinal plants, has anti-inflammatory, antioxidant, and anticancer activities. Celastrol has shown preventive/therapeutic effects in experimental models of several chronic diseases. These include, chronic inflammatory and autoimmune diseases (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, and psoriasis), neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis), atherosclerosis, obesity, Type 2 diabetes, and cancer...
2016: Advances in Experimental Medicine and Biology
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