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https://www.readbyqxmd.com/read/28728224/-antagonism-of-lovastatin-on-oxidative-stress-and-apoptosis-in-primary-rat-hippocampal-neurons-induced-by-%C3%AE-amyloid-peptide
#1
L C Tan, L Zhao, X H Liu, C M Deng, Z Z Guan
Objective: To investigate the effect of lovastatin on oxidative stress and apoptosis in neurons induced by β-amyloid peptide (Aβ). Methods: Primary culture of rat hippocampal neuron was treated with Aβ oligomers alone or combined with lovastatin. The levels of OH(-), H(2)O(2), O(2)·(-), malondialdehyde, superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities were measured by biochemical methods and protein expression of caspase-3 and bcl-2 was detected by Western blot. Results: As compared with the control group, treatment of 0...
July 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28728117/alzheimer-s-disease-markers-in-the-aged-sheep-ovis-aries
#2
Suzanne J Reid, Natasha E Mckean, Kristen Henty, Erik Portelius, Kaj Blennow, Skye R Rudiger, C Simon Bawden, Renee R Handley, Paul J Verma, Richard L M Faull, Henry J Waldvogel, Henrik Zetterberg, Russell G Snell
This study reports the identification and characterization of markers of Alzheimer's disease (AD) in aged sheep (Ovis aries) as a preliminary step toward making a genetically modified large animal model of AD. Importantly, the sequences of key proteins involved in AD pathogenesis are highly conserved between sheep and human. The processing of the amyloid-β (Aβ) protein is conserved between sheep and human, and sheep Aβ1-42/Aβ1-40 ratios in cerebrospinal fluid (CSF) are also very similar to human. In addition, total tau and neurofilament light levels in CSF are comparable with those found in human...
June 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28728104/design-synthesis-and-evaluation-of-coumarin-pargyline-hybrids-as-novel-dual-inhibitors-of-monoamine-oxidases-and-amyloid-%C3%AE-aggregation-for-the-treatment-of-alzheimer-s-disease
#3
Hua-Li Yang, Pei Cai, Qiao-Hong Liu, Xue-Lian Yang, Fan Li, Jin Wang, Jia-Jia Wu, Xiao-Bing Wang, Ling-Yi Kong
A series of coumarin-pargyline hybrids (4a-x) have been designed, synthesized and evaluated as novel dual inhibitors of Alzheimer's disease (AD). Most of the compounds exhibited a potent ability to inhibit amyloid-β (Aβ) aggregation and monoamine oxidases. In particular, compound 4x exhibited remarkable inhibitory activities against monoamine oxidases (IC50, 0.027 ± 0.004 μM for MAO-B; 3.275 ± 0.040 μM for MAO-A) and Aβ1-42 aggregation (54.0 ± 1.1%, 25 μM). Moreover, compound 4x showed low toxicity according to in vitro cell toxicity test...
July 8, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28727426/fully-atomistic-a%C3%AE-40-and-a%C3%AE-42-oligomers-in-water-observation-of-pore-like-conformations
#4
Matthew John Voelker, Bogdan Barz, Brigita Urbanc
Oligomers formed by amyloid β-protein (Aβ) are central to Alzheimer's disease (AD) pathology, yet their structure remains elusive. Of the two predominant Aβ alloforms, Aβ40 and Aβ42, the latter is more strongly associated with AD. Here, we structurally characterized Aβ40 and Aβ42 monomers through pentamers which were converted from previously derived coarse-grained (DMD4B-HYDRA) simulations into all-atom conformations and subjected to explicit-solvent MD. Free energy landscapes revealed that structural differences between Aβ40 and Aβ42 conformations increase with oligomer order up to trimers...
July 20, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28726016/amyloid-%C3%AE-derived-from-the-brain-of-the-alzheimer-s-disease-transgenic-mouse-is-resistant-to-proteolytic-digestion-due-to-its-conformation
#5
Baian Chen, Jing Zhang, Shubo Wang, Wen Wang, Zitong Yao, Quan Sun, Yi Wu, Jing Lu
The main pathological feature of Alzheimer's disease (AD) is the formation of abundant amyloid-β (Aβ) plaques in the human brain. Studies have reported that Aβ from the AD brain is resistant to proteolytic digestion, which may explain why Aβ cannot be readily eliminated from this organ. However, there are only a few studies that address this important question. We used the AD transgenic mouse (APP/PS1) model to show that Aβ derived from the brain of the old mouse is resistant to proteolytic digestion. This was in contrast to the proteinase K-sensitive human Aβ peptide, whose amino acid sequence was identical to that of AD mouse-derived Aβ but whose conformation was different (i...
July 19, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28724291/a-kinetic-model-for-two-step-nucleation-of-peptide-assembly
#6
Ming-Chien Hsieh, David G Lynn, Martha A Grover
Intermediate dynamic assemblies are increasingly seen as necessary for the initial desolvation and organization of biomaterials to achieve their final crystalline order, and here we present a general peptide assembly model for two-step nucleation. The model predicts the phase transitions and equilibria between different phases by a combination of the Flory-Huggins parameter, the particle growth constant, and the binding energy to the assemblies. Monte Carlo simulations are used to demonstrate how the system evolves from pure solution phases to the final thermodynamic assembly phase via a metastable particle phase...
July 19, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28722679/reversibility-of-a%C3%AE-oligomer-neurotoxicity
#7
EDITORIAL
Wataru Araki
No abstract text is available yet for this article.
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722194/effects-of-cholesterol-transport-inhibitor-u18666a-on-app-metabolism-in-rat-primary-astrocytes
#8
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/28721727/synthesis-of-intricate-fused-n-heterocycles-via-ring-rearrangement-metathesis
#9
Sambasivarao Kotha, Rama Gunta
Herein, a facile synthesis of intricate fused N-heterocycles has been disclosed by employing C-H activation and ring-rearrangement metathesis/enyne ring-rearrangement metathesis as key steps. Interestingly, some of these N-heterocyclic products possess the tricyclic core of epimeloscine, deoxycalyciphylline B, daphlongamine H, isodaphlongamine H and a bioactive alkaloid, annotinolide A, which shows anti-aggregation activity against amyloid-β (Aβ)1-42 peptide aggregation. Moreover, various starting materials required in this protocol are easily assembled via C-X bond annulation of 2-bromo-N-protected aniline with norbornadiene or directing group-assisted ruthenium-catalyzed C-H activation of N-methoxybenzamide...
July 19, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28720165/bdnf-val66met-in-preclinical-alzheimer-s-disease-is-associated-with-short-term-changes-in-episodic-memory-and-hippocampal-volume-but-not-serum-mbdnf
#10
Yen Ying Lim, Stephanie Rainey-Smith, Yoon Lim, Simon M Laws, Veer Gupta, Tenielle Porter, Pierrick Bourgeat, David Ames, Christopher Fowler, Olivier Salvado, Victor L Villemagne, Christopher C Rowe, Colin L Masters, Xin Fu Zhou, Ralph N Martins, Paul Maruff
BACKGROUND: The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism Met allele exacerbates amyloid (Aβ) related decline in episodic memory (EM) and hippocampal volume (HV) over 36-54 months in preclinical Alzheimer's disease (AD). However, the extent to which Aβ+ and BDNF Val66Met is related to circulating markers of BDNF (e.g. serum) is unknown. We aimed to determine the effect of Aβ and the BDNF Val66Met polymorphism on levels of serum mBDNF, EM, and HV at baseline and over 18-months...
July 19, 2017: International Psychogeriatrics
https://www.readbyqxmd.com/read/28720101/drug-candidates-in-clinical-trials-for-alzheimer-s-disease
#11
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/28719344/protective-effect-of-edaravone-against-a%C3%AE-25-35-induced-mitochondrial-oxidative-damage-in-sh-sy5y-cells
#12
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/28718623/a-multimodal-spectroscopic-imaging-method-to-characterize-the-metal-and-macromolecular-content-of-proteinaceous-aggregates-amyloid-plaques
#13
Kelly L Summers, Nicholas Fimognari, Ashley Hollings, Mitchell Kiernan, Virginie Lam, Rebecca J Tidy, David Paterson, Mark J Tobin, Ryu Takechi, Graham N George, Ingrid J Pickering, John C Mamo, Hugh H Harris, Mark J Hackett
Alzheimer's disease (AD) is a major international health and economic concern. A key pathological feature of AD is so-called "amyloid-β-plaques", or "Aβ-plaques", which are deposits of aggregated protein, enriched with the Aβ fragment of amyloid precursor protein. Despite their name, the deposits are not pure Aβ and have a heterogeneous, chemically complex composition that can include multiple proteins, lipids, and metal ions (Fe, Cu, or Zn). Despite extensive research, it is still uncertain whether Aβ-plaques are a cause or a consequence of AD pathology...
July 18, 2017: Biochemistry
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/28714389/a-peptide-based-pro-drug-ameliorates-amyloid-%C3%AE-induced-neuronal-apoptosis-in-in-vitro-sh-sy5y-cells
#15
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
#16
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
https://www.readbyqxmd.com/read/28714019/salidroside-protects-pc12-cells-from-a%C3%AE-1%C3%A2-40%C3%A2-induced-cytotoxicity-by-regulating-the-nicotinamide-phosphoribosyltransferase-signaling-pathway
#17
Xujiao Huang, Sanli Xing, Chuan Chen, Zhihua Yu, Jiulin Chen
Alzheimer's disease (AD) is the most common type of senile dementia, which often develops in elderly or presenile individuals. As one of the pathological features of AD, amyloid β‑protein (Aβ) causes energy dysmetabolism, thereby inducing cellular damage and apoptosis. Salidroside is the main active component of the traditional Chinese medicine Rhodiola. Previous studies have demonstrated that salidroside exerts a regulatory role in energy metabolism. However, the role and the mechanism of action of salidroside in AD remain unclear...
July 5, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713245/multifaceted-roles-of-metzincins-in-cns-physiology-and-pathology-from-synaptic-plasticity-and-cognition-to-neurodegenerative-disorders
#18
REVIEW
Patrycja Brzdak, Daria Nowak, Grzegorz Wiera, Jerzy W Mozrzymas
The extracellular matrix (ECM) and membrane proteolysis play a key role in structural and functional synaptic plasticity associated with development and learning. A growing body of evidence underscores the multifaceted role of members of the metzincin superfamily, including metalloproteinases (MMPs), A Disintegrin and Metalloproteinases (ADAMs), A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTSs) and astacins in physiological and pathological processes in the central nervous system (CNS)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28713158/amyloid-beta-structure-biology-and-structure-based-therapeutic-development
#19
REVIEW
Guo-Fang Chen, Ting-Hai Xu, Yan Yan, Yu-Ren Zhou, Yi Jiang, Karsten Melcher, H Eric Xu
Amyloid beta peptide (Aβ) is produced through the proteolytic processing of a transmembrane protein, amyloid precursor protein (APP), by β- and γ-secretases. Aβ accumulation in the brain is proposed to be an early toxic event in the pathogenesis of Alzheimer's disease, which is the most common form of dementia associated with plaques and tangles in the brain. Currently, it is unclear what the physiological and pathological forms of Aβ are and by what mechanism Aβ causes dementia. Moreover, there are no efficient drugs to stop or reverse the progression of Alzheimer's disease...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28712264/treadmill-exercise-ameliorates-the-regulation-of-energy-metabolism-in-skeletal-muscle-of-nse-ps2mtransgenic-mice-with-alzheimer-s-disease
#20
Jang-Soo Yook, Joon-Yong Cho
PURPOSE: Alzheimer's disease (AD) is classified as a progressive neurological disorder, which not only causes cognitive impairment but also abnormal weight loss, with a reduction of muscle mass related to the accumulation of amyloid-β (Aβ) in skeletal muscle. Thus, we investigated the effect of treadmill exercise on Aβ deposition, and p-AMPK, p-ACC, BDNF, and GLUT4 protein levels the regulation of muscle energy metabolism using an AD mouse. METHODS: At 13 months of age, NSE/PS2m mice (Tg) and control mice (non-Tg) were assigned to non-exercise control (Con) and exercise groups (Exe)...
March 31, 2017: Journal of Exercise Nutrition & Biochemistry
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