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https://www.readbyqxmd.com/read/29210129/effect-of-resveratrol-and-pterostilbene-on-aging-and-longevity
#1
REVIEW
Yi-Rong Li, Shiming Li, Chi-Chien Lin
Over the past years, several studies have found that foods rich in polyphenols protect against age-related disease, such as atherosclerosis, cardiovascular disease, cancer, arthritis, cataracts, osteoporosis, type 2 diabetes (T2D), hypertension and Alzheimer's disease. Resveratrol and pterostilbene, the polyphenol found in grape and blueberries, have beneficial effects as anti-aging compounds through modulating the hallmarks of aging, including oxidative damage, inflammation, telomere attrition and cell senescence...
December 6, 2017: BioFactors
https://www.readbyqxmd.com/read/29207114/elderly-apolipoprotein-e%C3%A2-%C3%A2-mice-with-advanced-atherosclerotic-lesions-in-the-aorta-do-not-develop-alzheimer-s-disease-like-pathologies
#2
Reut Shnerb Ganor, Dror Harats, Ginette Schiby, Kinneret Rosenblatt, Irit Lubitz, Aviv Shaish, Ophira Salomon
Atherosclerosis and Alzheimer's disease (AD) are a major cause of morbidity and mortality in Western societies. These diseases share common risk factors, which are exhibited in old age, including hypertension, diabetes, hypercholesterolemia and apolipoprotein (Apo) ε4 allele. We previously demonstrated that factor XI (FXI) deficiency in mice reduced the atherosclerotic plaque area in coronary sinuses and the aortic arch. This led us to investigate whether FXI deficiency in elderly ApoE knockout (KO) mice would decrease pathological alterations compatible with atherosclerosis and AD...
November 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29197144/protein-folding-by-water-soluble-cyclic-diselenides-with-novel-oxidoreductase-and-isomerase-activities
#3
Kenta Arai, Haruhito Ueno, Yuki Asano, Gaurango Chakrabarty, Shingo Shimodaira, Govindasamy Mugesh, Michio Iwaoka
Protein disulfide isomerase (PDI) family, present in the endoplasmic reticulum (ER) of mammalian cells, catalyzes the formation and cleavage of disulfide bonds and thereby helps in protein folding. A decrease in PDI activity under ER stress conditions lead to protein misfolding, which is responsible for the progression of various human diseases, such as Alzheimers, Parkinsons, diabetes mellitus and atherosclerosis. In this paper, we report that water-soluble cyclic diselenides mimic the multifunctional activity of PDI family by facilitating oxidative folding, disulfide formation/reduction and repair of the scrambled disulfide bonds in misfolded proteins...
December 2, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29195510/cerebrovascular-pathology-in-down-syndrome-and-alzheimer-disease
#4
Elizabeth Head, Michael J Phelan, Eric Doran, Ronald C Kim, Wayne W Poon, Frederick A Schmitt, Ira T Lott
People with Down syndrome (DS) are at high risk for developing Alzheimer disease (AD) with age. Typically, by age 40 years, most people with DS have sufficient neuropathology for an AD diagnosis. Interestingly, atherosclerosis and hypertension are atypical in DS with age, suggesting the lack of these vascular risk factors may be associated with reduced cerebrovascular pathology. However, because the extra copy of APP leads to increased beta-amyloid peptide (Aβ) accumulation in DS, we hypothesized that there would be more extensive and widespread cerebral amyloid angiopathy (CAA) with age in DS relative to sporadic AD...
December 1, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29193967/structure-guided-discovery-of-novel-potent-and-orally-bioavailable-inhibitors-of-lipoprotein-associated-phospholipase-a2
#5
Qiufeng Liu, Fubao Huang, Xiao-Jing Yuan, Kai Wang, Yi Zou, Jianhua Shen, Yechun Xu
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a promising therapeutic target for atherosclerosis, Alzheimer's disease and diabetic macular edema. Here we report the identification of novel sulfonamide scaffold Lp-PLA2 inhibitors derived from a relatively weak fragment. Similarity searching on this fragment followed by molecular docking leads to the discovery of a micromolar inhibitor with 300-fold potency improvement. By the application of a structure-guided design strategy, a successful hit-to-lead optimization was achieved and a number of Lp-PLA2 inhibitors with single-digit nanomolar activity were obtained...
December 1, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29163489/ameliorating-amyloid-%C3%AE-fibrils-triggered-inflammation-via-curcumin-loaded-polymeric-nanoconstructs
#6
Andrea Ameruoso, Roberto Palomba, Anna Lisa Palange, Antonio Cervadoro, Aeju Lee, Daniele Di Mascolo, Paolo Decuzzi
Inflammation is a common hallmark in several diseases, including atherosclerosis, cancer, obesity, and neurodegeneration. In Alzheimer's disease (AD), growing evidence directly correlates neuronal damage with inflammation of myeloid brain cells, such as microglia. Here, polymeric nanoparticles were engineered and characterized for the delivery of anti-inflammatory molecules to macrophages stimulated via direct incubation with amyloid-β fibers. 200 nm spherical polymeric nanoconstructs (SPNs) and 1,000 nm discoidal polymeric nanoconstructs (DPNs) were synthesized using poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), and lipid chains as building blocks...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29107848/treated-hypothyroidism-is-associated-with-cerebrovascular-disease-but-not-alzheimer-s-disease-pathology-in-older-adults
#7
Willa D Brenowitz, Fang Han, Walter A Kukull, Peter T Nelson
Thyroid hormone disease is common among older adults and is associated with cognitive impairment. However, pathologic correlates are not well understood. We studied pathologic and clinical factors associated with hypothyroidism, the most common manifestation of thyroid disease, in research subjects seen annually for clinical evaluations at U.S. Alzheimer's Disease Centers. Thyroid disease and treatment status were assessed during clinician interviews. Among autopsied subjects, there were 555 participants with treated hypothyroidism and 2146 without known thyroid disease; hypothyroidism was associated with severe atherosclerosis (odds ratio: 1...
November 3, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29093073/midlife-systemic-inflammatory-markers-are-associated-with-late-life-brain-volume-the-aric-study
#8
Keenan A Walker, Ron C Hoogeveen, Aaron R Folsom, Christie M Ballantyne, David S Knopman, B Gwen Windham, Clifford R Jack, Rebecca F Gottesman
OBJECTIVE: To clarify the temporal relationship between systemic inflammation and neurodegeneration, we examined whether a higher level of circulating inflammatory markers during midlife was associated with smaller brain volumes in late life using a large biracial prospective cohort study. METHODS: Plasma levels of systemic inflammatory markers (fibrinogen, albumin, white blood cell count, von Willebrand factor, and Factor VIII) were assessed at baseline in 1,633 participants (mean age 53 [5] years, 60% female, 27% African American) enrolled in the Atherosclerosis Risk in Communities Study...
November 1, 2017: Neurology
https://www.readbyqxmd.com/read/29051098/impact-of-tyrosine-nitration-at-positions-tyr307-and-tyr335-on-structural-dynamics-of-lipoprotein-associated-phospholipase-a2-a-therapeutically-important-cardiovascular-biomarker-for-atherosclerosis
#9
Arun Bahadur Gurung, Atanu Bhattacharjee
Protein tyrosine nitration (PTN) is a post translational event which results in the generation of 3-Nitrotyrosine (3-NT). High levels of 3-NT were reported in several human diseases such as Parkinson's disease, Alzheimer's disease, amylotrophic lateral sclerosis and coronary artery disease. It was reported that PTN at positions 307 and 335 of Lipoprotein-associated phospholipase A2 (Lp-PLA2) curtails its enzymatic activity but the mechanism of inhibition at the structure level is still incomprehensible. The present study is an in silico endeavor to understand nitrative stress induced structural changes in Lp-PLA2...
October 16, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29025764/higher-risk-of-vascular-dementia-in-myocardial-infarction-survivors
#10
Jens Sundbøll, Erzsébet Hováth-Puhó, Kasper Adelborg, Morten Schmidt, Lars Pedersen, Hans Erik Bøtker, Victor W Henderson, Henrik T Sørensen
Background -Increased risk of dementia after myocardial infarction (MI) may be mediated by shared risk factors (e.g., atherosclerosis) and post-MI stroke. We examined risk of dementia in 1-year survivors of MI. Methods -Using Danish medical registries, we conducted a nationwide population-based cohort study of all patients with first-time MI and a sex-, birth year-, and calendar year-matched general population comparison cohort without MI (1980-2012). Cox regression analysis was used to compute 1-35 year adjusted hazard ratios (aHRs) for dementia, controlled for matching factors and adjusted for comorbidities and socioeconomic status...
October 12, 2017: Circulation
https://www.readbyqxmd.com/read/29018129/neuroimaging-correlates-of-cerebral-microbleeds-the-aric-study-atherosclerosis-risk-in-communities
#11
MULTICENTER STUDY
Jonathan Graff-Radford, Jeannette Simino, Kejal Kantarci, Thomas H Mosley, Michael E Griswold, B Gwen Windham, A Richey Sharrett, Marilyn S Albert, Rebecca F Gottesman, Clifford R Jack, Prashanthi Vemuri, David S Knopman
BACKGROUND AND PURPOSE: Cerebral microbleed (CMB) location (deep versus strictly lobar) may elucidate underlying pathology with deep CMBs being more associated with hypertensive vascular disease and lobar CMBs being more associated with cerebral amyloid angiopathy. The objective of this study was to determine whether neuroimaging signs of vascular disease and Alzheimer pathology are associated with different types of CMBs. METHODS: Among 1677 nondemented ARIC (Atherosclerosis Risk in Communities) participants (mean age=76±5 years; 40% men; 26% black) with 3-Tesla MRI scans at the fifth examination (2011-2013), we fit multinomial logistic regression models to quantify relationships of brain volumes (Alzheimer disease signature regions, total gray matter, frontal gray matter, and white matter hyperintensity volumes), infarct frequencies (lacunar, nonlacunar, and total), and apolipoprotein E (number of ε4 alleles) with CMB location (none, deep/mixed, or strictly lobar CMBs)...
November 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28943355/boron-based-inhibitors-of-the-nlrp3-inflammasome
#12
Alex G Baldwin, Jack Rivers-Auty, Michael J D Daniels, Claire S White, Carl H Schwalbe, Tom Schilling, Halah Hammadi, Panichakorn Jaiyong, Nicholas G Spencer, Hazel England, Nadia M Luheshi, Manikandan Kadirvel, Catherine B Lawrence, Nancy J Rothwell, Michael K Harte, Richard A Bryce, Stuart M Allan, Claudia Eder, Sally Freeman, David Brough
NLRP3 is a receptor important for host responses to infection, yet is also known to contribute to devastating diseases such as Alzheimer's disease, diabetes, atherosclerosis, and others, making inhibitors for NLRP3 sought after. One of the inhibitors currently in use is 2-aminoethoxy diphenylborinate (2APB). Unfortunately, in addition to inhibiting NLRP3, 2APB also displays non-selective effects on cellular Ca(2+) homeostasis. Here, we use 2APB as a chemical scaffold to build a series of inhibitors, the NBC series, which inhibit the NLRP3 inflammasome in vitro and in vivo without affecting Ca(2+) homeostasis...
November 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28941727/intravenous-treatment-with-human-recombinant-apoa-i-milano-reduces-beta-amyloid-cerebral-deposition-in-the-app23-transgenic-mouse-model-of-alzheimer-s-disease
#13
Sofía Fernández-de Retana, Alex Montañola, Paula Marazuela, Maialen De La Cuesta, Aina Batlle, Marc Fatar, Saskia Grudzenski, Joan Montaner, Mar Hernández-Guillamon
Beyond the crucial role of apolipoprotein A-I (ApoA-I) on peripheral cholesterol metabolism, this apolipoprotein has also been implicated in beta amyloid (Aβ)-related neuropathologies. ApoA-I-Milano (M) is a mutated variant, which showed increased vasoprotective properties compared to ApoA-I-wild type in models of atherosclerosis and cardiovascular damage. We speculated that ApoA-I-M may also protect Aβ-affected vasculature and reverse some of the pathological features associated with Alzheimer's disease (AD)...
December 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28934192/metabolomics-and-cognition-in-african-american-adults-in-midlife-the-atherosclerosis-risk-in-communities-study
#14
J Bressler, B Yu, T H Mosley, D S Knopman, R F Gottesman, A Alonso, A R Sharrett, L M Wruck, E Boerwinkle
Clinical studies have shown alterations in metabolic profiles when patients with mild cognitive impairment and Alzheimer's disease dementia were compared to cognitively normal subjects. Associations between 204 serum metabolites measured at baseline (1987-1989) and cognitive change were investigated in 1035 middle-aged community-dwelling African American participants in the biracial Atherosclerosis Risk in Communities (ARIC) Study. Cognition was evaluated using the Delayed Word Recall Test (DWRT; verbal memory), the Digit Symbol Substitution Test (DSST; processing speed) and the Word Fluency Test (WFT; verbal fluency) at visits 2 (1990-1992) and 4 (1996-1998)...
July 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28916531/diabetes-prediabetes-and-brain-volumes-and-subclinical-cerebrovascular-disease-on-mri-the-atherosclerosis-risk-in-communities-neurocognitive-study-aric-ncs
#15
Andrea L C Schneider, Elizabeth Selvin, A Richey Sharrett, Michael Griswold, Josef Coresh, Clifford R Jack, David Knopman, Thomas Mosley, Rebecca F Gottesman
OBJECTIVE: To examine the associations of prediabetes, diabetes, and diabetes severity (as assessed by HbA1c and diabetes duration) with brain volumes and vascular pathology on brain MRI and to assess whether the associations of diabetes with brain volumes are mediated by brain vascular pathology. RESEARCH DESIGN AND METHODS: Cross-sectional study of 1,713 participants in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) (mean age 75 years, 60% female, 27% black, 30% prediabetes, and 35% diabetes) who underwent 3T brain MRI scans in 2011-2013...
November 2017: Diabetes Care
https://www.readbyqxmd.com/read/28901253/bacterial-toxins-a-hope-towards-angiogenic-ailments
#16
Rekha Khandia, Ashok Kumar Munjal, Kuldeep Dhama, Yashpal Singh Malik
Angiogenesis is a vital physiological process essential for growth and maintenance of the body. It plays an important role during embryonic development and generally absent in adults with some exceptions like during wound repair and menstrual cycle in women. Excess as well as deficiency in angiogenesis, result in pathological conditions. It is a tightly regulated process; rely on cascade of several molecular signalling pathways involving many effectors like VEGF, FGF, PDGF, IGF etc. Excessive angiogenesis is associated with disorders like tumor, atherosclerosis, rheumatoid arthritis, diabetic retinopathy, endometriosis, psoriasis, adiposity...
September 11, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28888831/steryl-ester-synthesis-storage-and-hydrolysis-a-contribution-to-sterol-homeostasis
#17
REVIEW
Martina Korber, Isabella Klein, Günther Daum
Sterols are essential lipids of all eukaryotic cells, appearing either as free sterols or steryl esters. Besides other regulatory mechanisms, esterification of sterols and hydrolysis of steryl esters serve to buffer both an excess and a lack of free sterols. In this review, the esterification process, the storage of steryl esters and their mobilization will be described. Several model organisms are discussed but the focus was set on mammals and the yeast Saccharomyces cerevisiae. The contribution of imbalanced cholesterol homeostasis to several human diseases, namely Wolman disease, cholesteryl ester storage disease, atherosclerosis and Alzheimer's disease, Niemann-Pick type C and Tangier disease is described...
December 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28810593/carotid-atherosclerosis-promotes-the-progression-of-alzheimer-s-disease-a-three-year-prospective-study
#18
Jing Xiang
Although cerebrovascular diseases have been considered as risk factors for cognitive decline and dementia, the associations between atherosclerosis and Alzheimer's disease (AD) have not been fully examined and remain controversial. The aim of this three-year prospective study was to investigate whether arotid artery atherosclerosis accelerates cognitive impairment in AD patients. The association of carotid intimal medial thickness (IMT) with prospective trajectories of cognitive function was assessed among 521 patients with light to moderate AD, and 437 AD patients were followed up annually for 3 years...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28800073/electronegative-low-density-lipoprotein-l5-impairs-viability-and-ngf-induced-neuronal-differentiation-of-pc12-cells-via-lox-1
#19
Jiz-Yuh Wang, Chiou-Lian Lai, Ching-Tien Lee, Chen-Yen Lin
There have been striking associations of cardiovascular diseases (e.g., atherosclerosis) and hypercholesterolemia with increased risk of neurodegeneration including Alzheimer's disease (AD). Low-density lipoprotein (LDL), a cardiovascular risk factor, plays a crucial role in AD pathogenesis; further, L5, a human plasma LDL fraction with high electronegativity, may be a factor contributing to AD-type dementia. Although L5 contributing to atherosclerosis progression has been studied, its role in inducing neurodegeneration remains unclear...
August 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28777829/identification-of-an-early-transcriptomic-signature-of-insulin-resistance-and-related-diseases-in-lymphomonocytes-of-healthy-subjects
#20
Alice Matone, Eleonora Derlindati, Luca Marchetti, Valentina Spigoni, Alessandra Dei Cas, Barbara Montanini, Diego Ardigò, Ivana Zavaroni, Corrado Priami, Riccardo C Bonadonna
Insulin resistance is considered to be a pathogenetic mechanism in several and diverse diseases (e.g. type 2 diabetes, atherosclerosis) often antedating them in apparently healthy subjects. The aim of this study is to investigate with a microarray based approach whether IR per se is characterized by a specific pattern of gene expression. For this purpose we analyzed the transcriptomic profile of peripheral blood mononuclear cells in two groups (10 subjects each) of healthy individuals, with extreme insulin resistance or sensitivity, matched for BMI, age and gender, selected within the MultiKnowledge Study cohort (n = 148)...
2017: PloS One
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