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Alzheimers and cholesterol

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https://www.readbyqxmd.com/read/28620033/scissor-sisters-regulation-of-adam10-by-the-tspanc8-tetraspanins
#1
REVIEW
Alexandra L Matthews, Justyna Szyroka, Richard Collier, Peter J Noy, Michael G Tomlinson
A disintegrin and metalloprotease 10 (ADAM10) is a ubiquitously expressed transmembrane protein which is essential for embryonic development through activation of Notch proteins. ADAM10 regulates over 40 other transmembrane proteins and acts as a 'molecular scissor' by removing their extracellular regions. ADAM10 is also a receptor for α-toxin, a major virulence factor of Staphylococcus aureus Owing to the importance of its substrates, ADAM10 is a potential therapeutic target for cancer, neurodegenerative diseases such as Alzheimer's and prion diseases, bacterial infection and inflammatory diseases such as heart attack, stroke and asthma...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28593141/glycosyl-chains-and-25-hydroxycholesterol-contribute-to-the-intracellular-transport-of-amyloid-beta-a%C3%AE-42-in-jurkat-t-cells
#2
Neha Sharma, KeangOK Baek, Huong T T Phan, Naofumi Shimokawa, Masahiro Takagi
Amyloid beta (Aβ) is a peptide responsible for the development of Alzheimer's disease (AD). Misfolding and accumulation of endogenous Aβ can lead to neural cell apoptosis through endoplasmic reticulum (ER) stress. Added exogenous Aβ can also result in ER stress, leading to neurotoxicity and apoptosis, which is identical to that caused by the endogenous peptide. We have speculated that the endocytic transport of Aβ causes ER stress and have previously shown that the oxysterol, in particular, 7-ketocholesterol (7-keto) induces more surface interaction between Aβ-42 and Jurkat cells than cholesterol...
June 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28584559/schisandrae-fructus-reduces-symptoms-of-4-vinylcyclohexene-diepoxide-induced-ovarian-failure-in-mice
#3
Dasom Shin, Jinhee Ha, Seong Bin Hong, Geun-Hyung Kang, Deok-Sang Hwang, Hyunsu Bae
Menopause is associated with a decrease in the level of sex hormones such as ovarian estradiol and progesterone and can cause various symptoms such as depression, hot flash, fatigue, heart palpitations, and headache. Furthermore, there is a risk of developing complications such as osteoporosis, cardiovascular diseases, Alzheimer's disease, and ovarian cancer. Schisandrae Fructus (SF) is widely used in Korean medicine as a cure for such complications. This study was conducted to evaluate the therapeutic effects of SF against menopause symptoms associated with follicle depletion caused by the industrial chemical 4-vinylcyclohexene diepoxide (VCD) in mice...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28582856/lipidomic-profiles-in-diabetes-and%C3%A2-dementia
#4
Kevin Huynh, Ralph N Martins, Peter J Meikle
Lipids are a diverse class of hydrophobic and amphiphilic molecules which make up the bulk of most biological systems and are essential for human life. The role of lipids in health and disease has been recognized for many decades, as evidenced by the early identification of cholesterol as an important risk factor of heart disease and the development and introduction of statins as a one of the most successful therapeutic interventions to date. While several studies have demonstrated an increased risk of dementia, including Alzheimer's disease (AD), in those with diabetes mellitus, the nature of this risk is not well understood...
May 30, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28578514/the-beneficial-effects-of-hmg-coa-reductase-inhibitors-in-the-processes-of-neurodegeneration
#5
REVIEW
Seyed Soheil Saeedi Saravi, Seyed Sobhan Saeedi Saravi, Alireza Arefidoust, Ahmad Reza Dehpour
Statins, cholesterol lowering drugs, have been demonstrated to exert beneficial effects in other conditions such as primary and progressing neurodegenerative diseases beyond their original role. Observation that statins ameliorate the neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS) and cerebral ischemic stroke, the neuroprotective effects of these drugs are thought to be linked to their anti-inflammatory, anti-oxidative, and anti-excitotoxic properties...
June 3, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28577227/-search-for-risk-genes-in-alzheimer-s-disease
#6
REVIEW
I Karaca, H Wagner, A Ramirez
Alzheimer's disease (AD) is the most common form of neurodegenerative dementia. The susceptibility to AD is determined by a complex interaction between genetic, epigenetic, and environmental factors. Herein, the risk that can be attributed to genetic factors is high (up to 80%). While most AD patients are sporadic, in rare families Mendelian mode of inheritance can be observed. In these rare familial cases, full penetrant mutations have been identified in APP, PSEN1, and PSEN2. Mutations in these three genes are however rarely found in sporadic AD...
June 2, 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28573213/chemoproteomic-profiling-of-bile-acid-interacting-proteins
#7
Shentian Zhuang, Qiang Li, Lirong Cai, Chu Wang, Xiaoguang Lei
Bile acids (BAs) are a family of endogenous metabolites synthesized from cholesterol in liver and modified by microbiota in gut. Being amphipathic molecules, the major function of BAs is to help with dietary lipid digestion. In addition, they also act as signaling molecules to regulate lipid and glucose metabolism as well as gut microbiota composition in the host. Remarkably, recent discoveries of the dedicated receptors for BAs such as FXR and TGR5 have uncovered a number of novel actions of BAs as signaling hormones which play significant roles in both physiological and pathological conditions...
May 24, 2017: ACS Central Science
https://www.readbyqxmd.com/read/28571786/biodegradation-of-7-ketocholesterol-by-rhodococcus-erythropolis-mtcc-3951-process-optimization-and-enzymatic-insights
#8
Shubhrima Ghosh, S K Khare
The oxidation of cholesterol results in the formation of oxysterols such as 7-ketocholesterol(7KC), which are implicated in a number of age-related disorders such as atherosclerosis, Alzheimers' disease and macular degeneration. Current modalities use antioxidants and other natural or synthetic molecules to reduce 7KC-induced cytotoxity. The alternative application of enzymes from microbial sources to degrade oxysterols in vitro and in vivo is an innovative approach. The present study aims to assess the potential of the bacteria Rhodococcus erythropolis MTCC 3951 in degrading 7KC and mining relevant enzymes involved...
May 29, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28548854/curcumin-protects-membranes-through-carpet-or-insertion-model-depending-on-hydration
#9
Richard J Alsop, Alexander Dhaliwal, Maikel C Rheinstadter
Curcumin is the main ingredient of turmeric, a common Indian spice. Curcumin shows a broad spectrum of effects, including anti-Alzheimer's and anti-oxidant properties. An interaction between curcumin and lipid membranes has been speculated as the root-cause, and the molecule is often proposed to `protect' the bilayer. However, the detailed molecular mechanism of this protection is disputed. There is evidence that curcumin either a) lies flat on the bilayer and provides a `carpet' for protection by forming a steric barrier, or b) inserts into the membrane and stiffens tails, thereby protecting against peptide insertion...
May 26, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28527218/the-mechanisms-of-action-of-curcumin-in%C3%A2-alzheimer-s-disease
#10
Mengxi Tang, Changiz Taghibiglou
Alzheimer's disease (AD) is a neurodegenerative disorder of the elderly. As the prevalence of AD rises in the 21st century, there is an urgent need for the development of effective pharmacotherapies. Currently, drug treatments target the symptoms of the disease and do not modify or halt the disease progress. Thus, natural compounds have been investigated for their ability to treat AD. This review examines the efficacy of curcumin, a polyphenol derived from turmeric herb, to treat AD. We summarize the in vivo and in vitro research describing the mechanisms of action in which curcumin modifies AD pathology: curcumin inhibits the formation and promotes the disaggregation of amyloid-β plaques, attenuates the hyperphosphorylation of tau and enhances its clearance, binds copper, lowers cholesterol, modifies microglial activity, inhibits acetylcholinesterase, mediates the insulin signaling pathway, and is an antioxidant...
May 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28523294/autophagy-in-aging-and-disease
#11
Mădălina Fîlfan, Raluca Elena Sandu, Alexandra Daniela Zăvăleanu, Andrei GreşiŢă, Daniela Gabriela Glăvan, Denissa Greta Olaru, Aurel Popa-Wagner
Autophagy is a catabolic degradation system used to destroy and recycle the unnecessary or damaged components of a cell. Autophagy is present at a basal level in all mammals and is regulated by some conditions, such as oxidative stress, starvation or hypoxia. In aged tissues, increased but also decreased expression of autophagy-specific proteins, Beclin 1, LC3, Atg5 and Atg7 has been reported. Likewise, it could be shown that the lifespan of yeast, nematodes and flies is prolonged by pharmacologically stimulated autophagy using exogenous administered spermidine...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28511119/effects-of-breviscapine-on-amyloid-beta-1-42-induced-alzheimer-s-disease-mice-a-hplc-qtof-ms-based-plasma-metabonomics-study
#12
Hongjun Xia, Lingling Wu, Mengying Chu, Huimin Feng, Chunliang Lu, Qinghe Wang, Minghai He, Xiaoqun Ge
Herba Erigerontis has long been used to cure apoplexy hemiplegia and precordial pain in China. In addition, the bioactivities of its total flavonoids-breviscapine included inhibiting amyloid beta (Aβ) fibril formation, antioxidation and metal chelating, which are beneficial to treat Alzheimer's disease (AD). Hence, A HPLC-QTOF-MS based plasma metabonomics approach was applied to investigate the neuroprotective effects of breviscapine on intracerebroventricular injection of aggregated Aβ 1-42 induced AD mice for the first time in the study...
July 1, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28488677/uninformed-consent-in-nutrigenomic-research
#13
A Cecile Jw Janssens, Eline M Bunnik, Wylie Burke, Maartje Hn Schermer
Genetic testing for personalizing diet and wellness programs is performed without extensive counseling that informs about the potential implications of knowing one's genotype status. Genetic counseling seems redundant for genes that impact the effect of diet on biomarkers such as cholesterol and blood pressure, but the same genes may have pleiotropic effects that cannot be ignored. A well-known example is the APOE gene, which is implicated in cholesterol regulation and is a major risk factor for Alzheimer's disease...
June 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28482635/the-anti-amyloid-%C3%AE-and-neuroprotective-properties-of-a-novel-tricyclic-pyrone-molecule
#14
Izumi Maezawa, Bende Zou, Jacopo Di Lucente, William S Cao, Conrado Pascual, Sahani Weerasekara, Man Zhang, Xinmin Simon Xie, Duy H Hua, Lee-Way Jin
There is an urgent unmet need for new therapeutics for Alzheimer's disease (AD), the most common cause of dementia in the elderly. Therapeutic approaches targeting amyloid-β (Aβ) and its downstream toxicities have become major strategies in AD drug development. We have taken a rational design approach and synthesized a class of tricyclic pyrone (TP) compounds that show anti-Aβ and other neuroprotective actions. The in vivo efficacy of a lead TP named CP2 to ameliorate AD-like pathologies has been shown in mouse models...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28474568/lipid-biomarkers-in-alzheimer-s-disease
#15
Amira Zarrouk, Meryam Debbabi, Maryem Bezine, El Mostafa Karym, Asmaa Badreddine, Olivier Rouaud, Thibault Moreau, Mustapha Cherkaoui-Malki, Mohamed El Ayeb, Boubker Nasser, Mohamed Hammami, Gérard Lizard
Alzheimer's disease (AD) is the most frequent form of dementia. It is characterized by three successive stages (preclinical, mild cognitive impairment (MCI), and dementia), which are determined with a panel of complementary tests including behavioral and biochemical tests and imaging methods. Currently accepted biomarkers of AD include levels of brain chemicals related to amyloid or tau, and imaging-derived estimates of the size and metabolic activity of specific brain regions. At the moment, the pathogenesis of AD is still poorly understood but some studies support a link between lipid metabolism disorders and AD...
May 4, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28462694/obesity-and-metabolic-syndrome-affects-the-cholinergic-transmission-and-cognitive-functions
#16
Martinelli Ilenia, Tomassoni Daniele, Moruzzi Michele, Traini Enea, Seyed Khosrow Tayebati
Worldwide, at least 2.8 million people die each year as a result of being overweight or obese, that causes about 35.8 million (2.3%) of global Disability-Adjusted Life Year (DALYs). Obesity leads to metabolic syndrome, a pathological condition characterized by adverse metabolic effects on blood pressure, cholesterol, triglycerides and insulin resistance. Population-based investigations have suggested that obesity and metabolic syndrome may be associated with poorer cognitive performance and could be considered a possible risk factor for vascular Dementia and Alzheimer's Disease...
April 28, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28461971/cholesterol-in-the-pathogenesis-of-alzheimer-s-parkinson-s-diseases-and-autism-link-to-synaptic-dysfunction
#17
A M Petrov, M R Kasimov, A L Zefirov
In our previous review, we described brain cholesterol metabolism in control conditions and in the case of some rare neurological pathologies linked to defects in the genes which are directly involved in the synthesis and/or traffic of cholesterol. Here, we have analyzed disruptions in cholesterol homeostasis in widespread neurodegenerative diseases (Alzheimer's and Parkinson's diseases) and autism spectrum disorders. We particularly focused on the synaptic dysfunctions that could arise from changes in both membrane cholesterol availability and oxysterol production...
January 2017: Acta Naturae
https://www.readbyqxmd.com/read/28456421/mendelian-randomization-implicates-high-density-lipoprotein-cholesterol-associated-mechanisms-in-etiology-of-age-related-macular-degeneration
#18
Stephen Burgess, George Davey Smith
PURPOSE: Undertake a systematic investigation into associations between genetic predictors of lipid fractions and age-related macular degeneration (AMD) risk. DESIGN: Two-sample Mendelian randomization investigation using published data. PARTICIPANTS: A total of 33 526 individuals (16 144 cases, 17 832 controls) predominantly of European ancestry from the International Age-related Macular Degeneration Genomics Consortium. METHODS: We consider 185 variants previously demonstrated to be associated with at least 1 of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglycerides at a genome-wide level of significance, and test their associations with AMD...
April 26, 2017: Ophthalmology
https://www.readbyqxmd.com/read/28444230/apoe-%C3%AE%C2%B54-%C3%AE%C2%B54-diminishes-neurotrophic-function-of-human-ipsc-derived-astrocytes
#19
Jing Zhao, Mary D Davis, Yuka Atagi, Mitsuru Shinohara, Neill R Graff-Radford, Steven G Younkin, Zbigniew K Wszolek, Takahisa Kanekiyo, Guojun Bu
The ε4 allele of the APOE gene encoding apolipoprotein E (apoE) is a strong genetic risk factor for aging-related cognitive decline as well as late-onset Alzheimer's disease (AD) compared to the common ε3 allele. In the central nervous system, apoE is produced primarily by astrocytes and functions in transporting lipids including cholesterol to support neuronal homeostasis and synaptic integrity. Although mouse models and corresponding primary cells have provided valuable tools for studying apoE isoform-dependent functions, recent studies have shown that human astrocytes have distinct gene expression profile compare with rodent astrocytes...
April 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28439555/structural-and-biochemical-differences-between-the-notch-and-the-amyloid-precursor-protein-transmembrane-domains
#20
Catherine L Deatherage, Zhenwei Lu, Brett M Kroncke, Sirui Ma, Jarrod A Smith, Markus W Voehler, Robert L McFeeters, Charles R Sanders
γ-Secretase cleavage of the Notch receptor transmembrane domain is a critical signaling event for various cellular processes. Efforts to develop inhibitors of γ-secretase cleavage of the amyloid-β precursor C99 protein as potential Alzheimer's disease therapeutics have been confounded by toxicity resulting from the inhibition of normal cleavage of Notch. We present biochemical and structural data for the combined transmembrane and juxtamembrane Notch domains (Notch-TMD) that illuminate Notch signaling and that can be compared and contrasted with the corresponding traits of C99...
April 2017: Science Advances
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