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https://www.readbyqxmd.com/read/28527218/the-mechanisms-of-action-of-curcumin-in%C3%A2-alzheimer-s-disease
#1
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
#2
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
#3
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...
May 10, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28488677/uninformed-consent-in-nutrigenomic-research
#4
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...
May 10, 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28438747/low-ldl-cholesterol-pcsk9-and-hmgcr-genetic-variation-and-risk-of-alzheimer-s-disease-and-parkinson-s-disease-mendelian-randomisation-study
#12
Marianne Benn, Børge G Nordestgaard, Ruth Frikke-Schmidt, Anne Tybjærg-Hansen
Objective To test the hypothesis that low density lipoprotein (LDL) cholesterol due to genetic variation in the genes responsible for LDL cholesterol metabolism and biosynthesis(PCSK9 and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), respectively) is associated with a high risk of Alzheimer's disease, vascular dementia, any dementia, and Parkinson's disease in the general population.Design Mendelian randomisation study.Setting Copenhagen General Population Study and Copenhagen City Heart Study.Participants 111 194 individuals from the Danish general population...
April 24, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28421328/association-of-adiponectin-leptin-and-resistin-with-inflammatory-markers-and-obesity-in-dementia
#13
Małgorzata Bednarska-Makaruk, Ałła Graban, Anna Wiśniewska, Wanda Łojkowska, Anna Bochyńska, Magdalena Gugała-Iwaniuk, Ksenia Sławińska, Agnieszka Ługowska, Danuta Ryglewicz, Hanna Wehr
The aim of the study was to determine the role of adiponectin, leptin and resistin in various types of dementia and to investigate their association with inflammatory markers, insulin resistance and abdominal obesity. In 205 patients with dementia [89 with Alzheimer's disease (AD), 47 with vascular dementia (VaD), 69 with mixed dementia (MD)], 113 persons with mild cognitive impairment and in 107 controls serum adiponectin, leptin and resistin levels, pro-inflammatory [interleukin-6 (IL-6), C-reactive protein (hsCRP) and chitotriosidase] and anti-inflammatory (25-OH vitamin D, HDL-cholesterol and paraoxonase 1) markers, as well as glucose metabolism parameters (glucose, insulin and HOMA-IR) were determined...
April 18, 2017: Biogerontology
https://www.readbyqxmd.com/read/28417263/rosuvastatin-attenuates-high-salt-and-cholesterol-diet-induced-neuroinflammation-and-cognitive-impairment-via-preventing-nuclear-factor-kappab-pathway
#14
Ibraheem Husain, Mohd Akhtar, Divya Vohora, Malik Zainul Abdin, Mohammad Islamuddin, Mohd Jawaid Akhtar, Abul Kalam Najmi
Recent attention is focused on the impact of diet on health and mental well-being. High-salt and cholesterol diet (HSCD) is known to be associated with neuroinflammation which is the predominant factor for neurodegenerative disease like Alzheimer disease (AD). In the present study, we examined the neuroprotective potential of rosuvastatin, an HMG-CoA reductase inhibitor against HSCD induced neuroinflammation and cognitive impairment. Our results demonstrated that HSCD-induced cognitive impairment as determined by Morris water maze (MWM) task...
April 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28413178/synthesized-a%C3%AE-42-caused-intracellular-oxidative-damage-leading-to-cell-death-via-lysosome-rupture
#15
Yuki Oku, Kazuma Murakami, Kazuhiro Irie, Jun Hoseki, Yasuyoshi Sakai
Neuronal cellular accumulation of amyloid beta peptide (Aβ) has been implicated in the pathogenesis of Alzheimer’s disease (AD). Intracellular accumulation of Aβ42, a toxic form of Aβ, was observed as an early event in AD patients. However, its contribution and the cellular mechanism of cell death remained unclear. We herein revealed the mechanism by which Aβ42 incorporated into cells leads to cell death by using chemically synthesized Aβ42 variants. The Aβ42 variant Aβ42 (E22P) which has an increased tendency to oligomerize, accumulated in lysosomes at an earlier stage than wild-type Aβ42, leading to higher ROS production and lysosomal membrane oxidation, and resulting in cell death...
April 12, 2017: Cell Structure and Function
https://www.readbyqxmd.com/read/28408965/phospholipase-c-related-catalytically-inactive-protein-can-regulate-obesity-a-state-of-peripheral-inflammation
#16
REVIEW
Yosuke Yamawaki, Kana Oue, Satomi Shirawachi, Satoshi Asano, Kae Harada, Takashi Kanematsu
Obesity is defined as abnormal or excessive fat accumulation. Chronic inflammation in fat influences the development of obesity-related diseases. Many reports state that obesity increases the risk of morbidity in many diseases, including hypertension, dyslipidemia, type 2 diabetes, coronary heart disease, stroke, sleep apnea, and breast, prostate and colon cancers, leading to increased mortality. Obesity is also associated with chronic neuropathologic conditions such as depression and Alzheimer's disease. However, there is strong evidence that weight loss reduces these risks, by limiting blood pressure and improving levels of serum triglycerides, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol...
February 2017: Japanese Dental Science Review
https://www.readbyqxmd.com/read/28399252/association-between-midlife-vascular-risk-factors-and-estimated-brain-amyloid-deposition
#17
Rebecca F Gottesman, Andrea L C Schneider, Yun Zhou, Josef Coresh, Edward Green, Naresh Gupta, David S Knopman, Akiva Mintz, Arman Rahmim, A Richey Sharrett, Lynne E Wagenknecht, Dean F Wong, Thomas H Mosley
Importance: Midlife vascular risk factors have been associated with late-life dementia. Whether these risk factors directly contribute to brain amyloid deposition is less well understood. Objective: To determine if midlife vascular risk factors are associated with late-life brain amyloid deposition, measured using florbetapir positron emission tomography (PET). Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC)-PET Amyloid Imaging Study, a prospective cohort study among 346 participants without dementia in 3 US communities (Washington County, Maryland; Forsyth County, North Carolina; and Jackson, Mississippi) who have been evaluated for vascular risk factors and markers since 1987-1989 with florbetapir PET scans in 2011-2013...
April 11, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28384414/alteration-of-high-density-lipoprotein-functionality-in-alzheimer-s-disease-patients
#18
Paméla Camponova, Aurélie Le Page, Hicham Berrougui, Julie Lamoureux, Graham Pawelec, M Jacek Witkowski, Tamas Fulop, Abdelouahed Khalil
The aims of the present study were to determine whether high-density lipoprotein (HDL) functionality-mediated cholesterol efflux is altered in Alzheimer's disease and to investigate the role and effect of amyloid-beta (Aβ) in the regulation of the anti-atherogenic activity of HDL. Eighty-seven elderly subjects were recruited, of whom 27 were healthy, 27 had mild cognitive impairment (MCI), and 33 had mild Alzheimer's disease (mAD). Our results showed that total cholesterol levels are negatively correlated with the Mini-Mental State Examination (MMSE) score (r = -0...
April 6, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28373057/lysophosphatidylcholine-export-by-human-abca7
#19
Maiko Tomioka, Yoshinobu Toda, Noralyn B Mañucat, Hiroyasu Akatsu, Manabu Fukumoto, Nozomu Kono, Hiroyuki Arai, Noriyuki Kioka, Kazumitsu Ueda
The ATP-binding cassette transporter A7 (ABCA7), which is highly expressed in the brain, is associated with the pathogenesis of Alzheimer's disease (AD). However, the physiological function of ABCA7 and its transport substrates remain unclear. Immunohistochemical analyses of human brain sections from AD and non-AD subjects revealed that ABCA7 is expressed in neuron and microglia cells in the cerebral cortex. The transport substrates and acceptors were identified in BHK/ABCA7 cells and compared with those of ABCA1...
March 31, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28366823/redox-status-of-serum-apolipoprotein-e-and-its-impact-on-hdl-cholesterol-levels
#20
Kazuyoshi Yamauchi, Yuka Ebihara, Yasushi Kawakami
BACKGROUND: Apolipoprotein E (apoE) is closely involved in the pathogenesis of apoE-related diseases, such as Alzheimer's disease and cardiovascular disease. The redox modulation of cysteine-thiols in a protein is involved in various pathophysiological regulations; however, that of apoE has not been studied in detail. Herein, we devised an analytical method to determine the redox status of serum apoE and assessed its relation to serum cholesterol levels and apoE phenotype. METHODS: The present method was based on a band shift assay, using a photocleavable maleimide-conjugated polyethylene glycol...
March 30, 2017: Clinical Biochemistry
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