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https://www.readbyqxmd.com/read/28723664/detecting-the-genetic-link-between-alzheimer-s-disease-and-obesity-using-bioinformatics-analysis-of-gwas-data
#1
Qi-Shuai Zhuang, Hao Zheng, Xiao-Dan Gu, Liang Shen, Hong-Fang Ji
Alzheimer's disease (AD) represents the major form of dementia in the elderly. In recent years, accumulating evidence indicate that obesity may act as a risk factor for AD, while the genetic link between the two conditions remains unclear. This bioinformatics analysis aimed to detect the genetic link between AD and obesity on single nucleotide polymorphisms (SNPs), gene, and pathway levels based on genome-wide association studies data. A total of 31 SNPs were found to be shared by AD and obesity, which were linked to 7 genes...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723617/small-molecular-floribundiquinone-b-derived-from-medicinal-plants-inhibits-acetylcholinesterase-activity
#2
Bing Niu, Mengying Zhang, Pu Du, Li Jiang, Rui Qin, Qiang Su, Fuxue Chen, Dongshu Du, Yilai Shu, Kuo-Chen Chou
Being a neurodegenerative disorder, Alzheimer's disease (AD) is the one of the most terrible diseases. And acetylcholinesterase (AChE) is considered as an important target for treating AD. Acetylcholinesterase inhibitors (AChEI) are considered to be one of the effective drugs for the treatment of AD. The aim of this study is to find a novel potential AChEI as a drug for the treatment of AD. In this study, instead of using the synthetic compounds, we used those extracted from plants to investigate the interaction between floribundiquinone B (FB) and AChE by means of both the experimental approach such as fluorescence spectra, ultraviolet-visible (UV-vis) absorption spectrometry, circular dichroism (CD) and the theoretical approaches such as molecular docking...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722194/effects-of-cholesterol-transport-inhibitor-u18666a-on-app-metabolism-in-rat-primary-astrocytes
#3
Hongyan Yang, Yanlin Wang, Satyabrata Kar
Amyloid β (Aβ) peptides generated from the amyloid precursor protein (APP) play an important role in the degeneration of neurons and development of Alzheimer's disease (AD). Current evidence indicates that high levels of cholesterol-which increase the risk of developing AD-can influence Aβ production in neurons. However, it remains unclear how altered level/subcellular distribution of cholesterol in astrocytes can influence APP metabolism. In this study, we evaluated the effects of cholesterol transport inhibitor U18666A-a class II amphiphile that triggers redistribution of cholesterol within the endosomal-lysosomal (EL) system-on APP levels and metabolism in rat primary cultured astrocytes...
July 19, 2017: Glia
https://www.readbyqxmd.com/read/28721826/clinical-uses-of-melatonin-in-neurological-diseases-and-mental-and-behavioural-disorders
#4
Emilio J Sánchez-Barceló, Noemi R Revilla, María D Mediavilla, Carmen Martínez-Cué, Russel J Reiter
Melatonin is a molecule with numerous properties applicable to the treatment of neurological diseases. Among these properties are the following: potent scavenger of oxygen and nitrogen reactive species, anti-inflammatory features, immuno-enhancing nature, and modulation of circadian rhythmicity. Furthermore, low concentrations of melatonin are usually found in patients with neurological diseases and mental disorders. The positive results obtained in experimental models of diverse pathologies, including diseases of the nervous system (e...
July 18, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28721811/moving-to-the-rhythm-with-clock-circadian-genes-autophagy-mtor-and-sirt1-in-degenerative-disease-and-cancer
#5
Kenneth Maiese
BACKGROUND: The mammalian circadian clock and its associated clock genes are increasingly be recognized as critical components for a number of physiological and disease processes that extend beyond hormone release, thermal regulation, and sleep-wake cycles. New evidence suggests that clinical behavior disruptions that involve prolonged shift work and even space travel may negatively impact circadian rhythm and lead to multi-system disease. METHODS: In light of the significant role circadian rhythm can hold over the body's normal physiology as well as disease processes, we examined and discussed the impact circadian rhythm and clock genes hold over lifespan, neurodegenerative disorders, and tumorigenesis...
July 17, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28720101/drug-candidates-in-clinical-trials-for-alzheimer-s-disease
#6
REVIEW
Shih-Ya Hung, Wen-Mei Fu
Alzheimer's disease (AD) is a major form of senile dementia, characterized by progressive memory and neuronal loss combined with cognitive impairment. AD is the most common neurodegenerative disease worldwide, affecting one-fifth of those aged over 85 years. Recent therapeutic approaches have been strongly influenced by five neuropathological hallmarks of AD: acetylcholine deficiency, glutamate excitotoxicity, extracellular deposition of amyloid-β (Aβ plague), formation of intraneuronal neurofibrillary tangles (NTFs), and neuroinflammation...
July 19, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28719625/differences-of-immune-disorders-between-alzheimer-s-disease-and-breast-cancer-based-on-transcriptional-regulation
#7
Wei Kong, Xiaoyang Mou, Jin Deng, Benteng Di, Ruxing Zhong, Shuaiqun Wang, Yang Yang, Weiming Zeng
Although chronic inflammation and immune disorders are of great importance to the pathogenesis of both dementia and cancer, the pathophysiological mechanisms are not clearly understood. In recent years, growing epidemiological evidence and meta-analysis data suggest an inverse association between Alzheimer's disease (AD), which is the most common form of dementia, and cancer. It has been revealed that some common genes and biological processes play opposite roles in AD and cancer; however, the biological immune mechanism for the inverse association is not clearly defined...
2017: PloS One
https://www.readbyqxmd.com/read/28719622/characterization-of-plasma-metal-profiles-in-alzheimer-s-disease-using-multivariate-statistical-analysis
#8
Chunmei Guan, Rui Dang, Yu Cui, Liyan Liu, Xiaobei Chen, Xiaoyu Wang, Jingli Zhu, Donggang Li, Junwei Li, Decai Wang
The exact cause of Alzheimer's disease (AD) and the role of metals in its etiology remain unclear. We have used an analytical approach, based on inductively coupled plasma mass spectrometry coupled with multivariate statistical analysis, to study the profiles of a wide range of metals in AD patients and healthy controls. AD cannot be cured and the lack of sensitive biomarkers that can be used in the early stages of the disease may contribute to this treatment failure. In the present study, we measured plasma levels of amyloid-β1-42(0...
2017: PloS One
https://www.readbyqxmd.com/read/28719359/levodopa-in-parkinson-s-disease-a-review-of-population-pharmacokinetics-pharmacodynamics-analysis
#9
Amélie Marsot, Romain Guilhaumou, Jean Philippe Azulay, Olivier Blin
BACKGROUND: Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease. Although levodopa remains the single effective agent in the management of Parkinson's disease, the accurate determination of this optimal dosage is complicated by marked between-subject and between-occasion variability in this population.  This review presents a synthesis of the population pharmacokinetic and pharmacodynamic models of levodopa described in Parkinson's disease...
2017: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28719344/protective-effect-of-edaravone-against-a%C3%AE-25-35-induced-mitochondrial-oxidative-damage-in-sh-sy5y-cells
#10
G-L Zhang, L Zhang, Y-Y Guo, Z-L Ma, H-Y Wang, T Li, J Liu, Y Du, L Yao, T-T Li, J-M Du
Amyloid-β (Aβ)-induced oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD). Recent studies show that Aβ accumulation may lead to mitochondrial oxidative damage. In the present study, we investigated the protective effect of edaravone on mitochondrial damage in SH-SY5Y cells treated with Aβ25-35. SH-SY5Y cells were pre-treated with 20, 40 or 80 μM edaravone before treatment with 25 μM Aβ25-35. After 24h cell culture, cellular apoptosis, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), ATP levels and mitochondrial morphology were evaluated...
May 20, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28718678/discovery-of-novel-isoflavone-derivatives-as-ache-buche-dual-targeted-inhibitors-synthesis-biological-evaluation-and-molecular-modelling
#11
Bo Feng, Xinpeng Li, Jie Xia, Song Wu
AChE and BuChE are druggable targets for the discovery of anti-Alzheimer's disease drugs, while dual-inhibition of these two targets seems to be more effective. In this study, we synthesised a series of novel isoflavone derivatives based on our hit compound G from in silico high-throughput screening and then tested their activities by in vitro AChE and BuChE bioassays. Most of the isoflavone derivatives displayed moderate inhibition against both AChE and BuChE. Among them, compound 16 was identified as a potent AChE/BuChE dual-targeted inhibitor (IC50: 4...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28716886/clinical-neurology-and-epidemiology-of-the-major-neurodegenerative-diseases
#12
Michael G Erkkinen, Mee-Ohk Kim, Michael D Geschwind
Neurodegenerative diseases are a common cause of morbidity and cognitive impairment in older adults. Most clinicians who care for the elderly are not trained to diagnose these conditions, perhaps other than typical Alzheimer's disease (AD). Each of these disorders has varied epidemiology, clinical symptomatology, laboratory and neuroimaging features, neuropathology, and management. Thus, it is important that clinicians be able to differentiate and diagnose these conditions accurately. This review summarizes and highlights clinical aspects of several of the most commonly encountered neurodegenerative diseases, including AD, frontotemporal dementia (FTD) and its variants, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and Huntington's disease (HD)...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28715867/therapeutic-impact-of-grape-leaves-polyphenols-on-certain-biochemical-and-neurological-markers-in-alcl3-induced-alzheimer-s-disease
#13
Ibrahim H Borai, Magda K Ezz, Maha Z Rizk, Hanan F Aly, Mahmoud El-Sherbiny, Azza A Matloub, Ghadha I Fouad
Alzheimer's disease (AD) is a grave and prevailing neurodegenerative disease, characterized by slow and progressive neurodegeneration in different brain regions. Aluminum (Al) is a potent and widely distributed neurotoxic metal, implicated in the neuropathogenesis of AD. This study aimed to evaluate the possible neurorestorative potential of Vitis vinifera Leaves Polyphenolic (VLP) extract in alleviating aluminum chloride (AlCl3)-induced neurotoxicity in male rats. AlCl3 neurotoxicity induced a significant decrease in brain/serum acetylcholine (ACh) contents and serum dopamine (DA) levels, along with a significant increment of brain/serum acetylcholinesterase (AChE) activities...
July 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28715596/influence-of-physical-exercise-on-%C3%AE-amyloid-%C3%AE-synuclein-and-tau-accumulation-an-in-vitro-model-of-oxidative-stress-in-human-red-blood-cells
#14
C Iofrida, S Daniele, D Pietrobono, J Fusi, F Galetta, M L Trincavelli, U Bonuccelli, F Franzoni, C Martini
A common pathological feature of neurodegenerative disorders (NDs), such as Alzheimer's (AD) and Parkinson's (PD) diseases, is the abnormal accumulation and misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid1-42 (Aβ) and tau, in brain and in peripheral tissues too. Oxidative stress has been proved to be involved in NDs at various levels and, in particular, in such protein alterations, on the contrary physical activity is emerging as a counteracting factor in NDs. In the present work, the content of Aβ, α-syn and tau in red blood cells (RBCs) derived from ten endurance athletes (ATHL) and ten sedentary volunteers (SED) were compared before and after in vitrooxidative stress treatment...
July 1, 2017: Archives Italiennes de Biologie
https://www.readbyqxmd.com/read/28715462/cell-specificity-dictates-similarities-in-gene-expression-in-multiple-sclerosis-parkinson-s-disease-and-alzheimer-s-disease
#15
Yuichiro Itoh, Rhonda R Voskuhl
Drug repurposing is an efficient approach in new treatment development since it leverages previous work from one disease to another. While multiple sclerosis (MS), Parkinson's disease (PD), and Alzheimer's disease (AD) are all neurodegenerative diseases of the central nervous system (CNS) and differ in many clinical and pathological aspects, it is possible that they may share some mechanistic features. We hypothesized that focusing on gene expression in a CNS cell type specific manner might uncover similarities between diseases that could be missed using whole tissue gene expression analyses...
2017: PloS One
https://www.readbyqxmd.com/read/28714419/design-of-multi-target-agents-for-the-treatment-of-alzheimer-s-disease-based-on-tacrine
#16
Hongzhi Lin, Qi Li, Kai Gu, Jie Zhu, Xueyang Jiang, Yao Chen, Haopeng Sun
Alzheimer's disease (AD) is one of the most common forms of dementia in elderly people. To date, efficacious therapeutic agent for the treatment of AD is still very limited, so it has long been a challenging and attractive task to discover new anti-AD drugs. Considering the multifactorial nature of AD, recently, the concept of multi-target-directed ligands (MTDLs) has emerged as a new strategy for designing therapeutic agents on AD. MTDLs are believed to exert their effects through simultaneously affecting multiple targets which contribute to etiology of AD...
July 17, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28714400/cholinesterase-inhibitory-activity-of-some-semi-rigid-spiro-heterocycles-pom-analyses-and-crystalline-structure-of-pharmacophore-site
#17
Taibi Ben Hadda, Oualid Talhi, Artur S M Silva, Fatma Sezer Senol, Ilkay Erdogan Orhan, Abdur Rauf, Yahia N Mabkhot, Khaldoun Bachari, Ismail Warad, Thoraya A Farghaly, Ismail I Althagafi, Mohammad S Mubarak
Cholinesterase family consists of two sister enzymes; acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) which hydrolyze acetylcholine. Since deficit of acetylcholine has been evidenced in the patients of Alzheimer's disease (AD), cholinesterase inhibitors are currently the most prescribed drug class for the treatment of AD. In the present study, five compounds (2-6) with spiro skeleton have been synthesized and tested for their inhibitory potential in vitro against AChE and BChE using ELISA microtiter plate assays at 25 mg/mL...
July 13, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28714393/interrelationships-between-gut-microbiota-and-host-paradigms-role-in-neurodegenerative-diseases-and-future-prospects
#18
Javier Caballero- Villarraso, Alberto Galvan, Begoña M Escribano, Isaac Túnez
Advances in the knowledge of the microbiota and concepts related to it have triggered a wake-up call in biomedicine. The development in various scientific areas has enabled a better and broader approach to everything concerning the set of families of microorganisms that coexist with an individual and are able to function as one more organ in its body. Among the aforementioned scientific areas, those worth mentioning are the advances/progress in biotechnological resources and, in particular, molecular biology and related areas...
July 14, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28714389/a-peptide-based-pro-drug-ameliorates-amyloid-%C3%AE-induced-neuronal-apoptosis-in-in-vitro-sh-sy5y-cells
#19
Sourav Kumar, Ashim Paul, Sourav Kalita, Awanish Kumar, Saurabh Srivastav, Somoday Hazra, Anup Kumar Ghosh, Bhubaneswar Mandal, Amal Chandra Mondal
BACKGROUND: Alzheimer's disease (AD), a common protein misfolding neurodegenerative disorder, is one of the most common forms of dementia. Amyloid precursor protein (APP) derived amyloid-β (Aβ) proteins accumulated into interneuronal spaces and plays a crucial role in the disease progression and its pathology. The aggregated Aβ exerts its neurotoxic effects by inducing apoptosis and oxidative damage in neuronal cells. OBJECTIVES: We have investigated the effects of a synthesized Pro-Drug peptide (PDp) on Aβ1-40 induced cytotoxicity in human neuroblastoma SH-SY5Y cells, represents one of the most effective strategies in combating human AD...
July 13, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28714246/carbon-nanodot-sensitized-modulation-of-alzheimer-s-%C3%AE-amyloid-self-assembly-disassembly-and-toxicity
#20
You Jung Chung, Kayoung Kim, Byung Il Lee, Chan Beum Park
The self-assembly of amyloidogenic peptides into β-sheet-rich aggregates is a general feature of many neurodegenerative diseases, including Alzheimer's disease, which signifies the need for the effective attenuation of amyloid aggregation toward alleviating amyloid-associated neurotoxicity. This study reports that photoluminescent carbon nanodots (CDs) can effectively suppress Alzheimer's β-amyloid (Aβ) self-assembly and function as a β-sheet breaker disintegrating preformed Aβ aggregates. This study synthesizes CDs using ammonium citrate through one-pot hydrothermal treatment and passivates their surface with branched polyethylenimine (bPEI)...
July 17, 2017: Small
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