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amyloid oligomer

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https://www.readbyqxmd.com/read/28822725/berberine-modulates-amyloid-%C3%AE-peptide-generation-by-activating-amp-activated-protein-kinase
#1
Haijing Zhang, Chunhui Zhao, Guoqiong Cao, Limin Guo, Shuai Zhang, Yuexia Liang, Chunxia Qin, Ping Su, Hang Li, Wensheng Zhang
Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by memory deficits and cognitive decline. Excessive amyloid-β (Aβ) peptide aggregates and forms soluble oligomers and insoluble cerebral amyloid plaques, which is widely thought to be the underlying pathogenic mechanism of AD. Therefore, effective regulation of Aβ metabolism is an important aspect of preventing and improving AD. Berberine, which is the main active component of the traditional medicinal herb Coptidis rhizoma, has a positive effect on reducing Aβ levels...
August 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28821400/alzheimer-s-disease-as-oligomeropathy
#2
REVIEW
Kenjiro Ono
Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder and is characterized by pathological aggregates of amyloid β-protein (Aβ) and tau protein. On the basis of genetic evidence, biochemical data, and animal models, Aβ has been suggested to be responsible for the pathogenesis of AD (the amyloid hypothesis). Aβ molecules tend to aggregate to form oligomers, protofibrils, and mature fibrils. Although mature fibrils in the final stage have been thought to be the cause of AD pathogenesis, recent studies using synthetic Aβ peptides, a cell culture model, Aβ precursor protein transgenic mice models, and human samples, such as cerebrospinal fluids and postmortem brains of AD patients, suggest that pre-fibrillar forms (oligomers of Aβ) are more deleterious than are extracellular fibril forms...
August 16, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28821008/trans-caryophyllene-inhibits-amyloid-%C3%AE-a%C3%AE-oligomer-induced-neuroinflammation-in-bv-2-microglial-cells
#3
Yawei Hu, Ziling Zeng, Baojie Wang, Shougang Guo
Amyloid β (Aβ) is the major component of senile plaques (SP) in the brains of Alzheimer's disease (AD) patients, and serves as an inflammatory stimulus for microglia. Trans-caryophyllene (TC), a major component in the essential oils derived from various species of medicinal plants, has displayed its neuro-protective effects in previous studies. However, whether TC has a protective role in AD remains unknown. In this study, the effects of TC on Aβ1-42-induced neuro-inflammation were investigated. We found that TC reduced the release of LDH in BV-2 microglial cells treated with Aβ1-42...
August 15, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28818091/non-canonical-soluble-amyloid-beta-aggregates-and-plaque-buffering-controversies-and-future-directions-for-target-discovery-in-alzheimer-s-disease
#4
REVIEW
David L Brody, Hao Jiang, Norelle Wildburger, Thomas J Esparza
The specific amyloid-beta (Aβ) species or other amyloid-precursor protein cleavage products that are most directly related to human neurodegeneration and clinical dementia of the Alzheimer's type have not yet been directly identified. Without a clear understanding of the most relevant species, it is difficult to determine whether therapeutic candidates successfully engaged the correct target(s). Here, we review some of the controversies regarding soluble Aβ aggregates (also termed oligomers, dimers, trimers, Aβ*56, amylospheroids, etc...
August 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28817283/the-effects-of-a21g-mutation-on-transmembrane-amyloid-beta-11-40-trimer-an-in-silico-study
#5
Son Tung Ngo, Minh Tung Nguyen, Nguyen Thanh Nguyen, Van V Vu
Familial Alzheimer's disease (FAD) is passed down in family, which account for 2-3% of about 40 million AD cases worldwide. The Flemish (A21G) mutant of amyloid β (Aβ) exhibits unique properties among all hereditary mutants of FAD, including lowest aggregation rate. Recent studies showed that Aβ oligomers play key role in Alzheimer's disease (AD) pathogenesis. They could insert themselves in brain cell membrane, disrupting the membrane integrity and ion homeostasis. However, experimental studies of transmembrane Aβ oligomers have been limited due to their intrinsic heterogeneity...
August 17, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28812278/monomer-dependent-secondary-nucleation-in-amyloid-formation
#6
REVIEW
Sara Linse
Secondary nucleation of monomers on the surface of an already existing aggregate that is formed from the same kind of monomers may lead to autocatalytic amplification of a self-assembly process. Such monomer-dependent secondary nucleation occurs during the crystallization of small molecules or proteins and self-assembled materials, as well as in protein self-assembly into fibrous structures. Indications of secondary nucleation may come from analyses of kinetic experiments starting from pure monomers or monomers supplemented with a low concentration of pre-formed aggregates (seeds)...
August 15, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28811318/the-%C3%AE-cell-assassin-iapp-cytotoxicity
#7
Daniel Raleigh, Xiaoxue Zhang, Benoit Hastoy, Anne Clark
Islet amyloid polypeptide (IAPP) forms cytotoxic oligomers and amyloid fibrils in islets in Type 2 diabetes (T2DM). The causal factors for amyloid formation are largely unknown. Mechanisms of molecular folding and assembly of human IAPP (hIAPP) into β-sheets, oligomers and fibrils have been assessed by detailed biophysical studies of hIAPP and non-fibrillogenic, rodent IAPP (rIAPP); cytotoxicity is associated with the early phases (oligomers/multimers) of fibrillogenesis. Interaction with synthetic membranes promotes β-sheet assembly possibly via a transient α-helical molecular conformation...
August 15, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28806762/a-becn1-mutation-mediates-hyperactive-autophagic-sequestration-of-amyloid-oligomers-and-improved-cognition-in-alzheimer-s-disease
#8
Altea Rocchi, Soh Yamamoto, Tabitha Ting, Yuying Fan, Katherine Sadleir, Yigang Wang, Weiran Zhang, Sui Huang, Beth Levine, Robert Vassar, Congcong He
Impairment of the autophagy pathway has been observed during the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder characterized by abnormal deposition of extracellular and intracellular amyloid β (Aβ) peptides. Yet the role of autophagy in Aβ production and AD progression is complex. To study whether increased basal autophagy plays a beneficial role in Aβ clearance and cognitive improvement, we developed a novel genetic model to hyperactivate autophagy in vivo. We found that knock-in of a point mutation F121A in the essential autophagy gene Beclin 1/Becn1 in mice significantly reduces the interaction of BECN1 with its inhibitor BCL2, and thus leads to constitutively active autophagy even under non-autophagy-inducing conditions in multiple tissues, including brain...
August 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28801684/structural-properties-of-human-iapp-dimer-in-membrane-environment-studied-by-all-atom-molecular-dynamics-simulations
#9
Na Liu, Mojie Duan, Minghui Yang
The aggregation of human islet amyloid polypeptide (hIAPP) can damage the membrane of the β-cells in the pancreatic islets and induce type 2 diabetes (T2D). Growing evidences indicated that the major toxic species are small oligomers of IAPP. Due to the fast aggregation nature, it is hard to characterize the structures of IAPP oligomers by experiments, especially in the complex membrane environment. On the other side, molecular dynamics simulation can provide atomic details of the structure and dynamics of the aggregation of IAPP...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801274/mannich-base-approach-to-5-methoxyisatin-3-4-isopropylphenyl-hydrazone-a-water-soluble-prodrug-for-a-multitarget-inhibition-of-cholinesterases-beta-amyloid-fibrillization-and-oligomer-induced-cytotoxicity
#10
Leonardo Pisani, Annalisa De Palma, Nicola Giangregorio, Daniela V Miniero, Paolo Pesce, Orazio Nicolotti, Francesco Campagna, Cosimo D Altomare, Marco Catto
Targeting protein aggregation for the therapy of neurodegenerative diseases remains elusive for medicinal chemists, despite a number of small molecules known to interfere in amyloidogenesis, particularly of amyloid beta (Aβ) protein. Starting from previous findings in the antiaggregating activity of a class of indolin-2-ones inhibiting Aβ fibrillization, 5-methoxyisatin 3-(4-isopropylphenyl)hydrazone 1 was identified as a multitarget inhibitor of Aβ aggregation and cholinesterases with IC50s in the low μM range...
August 8, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28798664/interplay-of-energetics-and-er-stress-exacerbates-alzheimer-s-amyloid-%C3%AE-a%C3%AE-toxicity-in-yeast
#11
Xin Chen, Markus M M Bisschops, Nisha R Agarwal, Boyang Ji, Kumaravel P Shanmugavel, Dina Petranovic
Alzheimer's disease (AD) is a progressive neurodegeneration. Oligomers of amyloid-β peptides (Aβ) are thought to play a pivotal role in AD pathogenesis, yet the mechanisms involved remain unclear. Two major isoforms of Aβ associated with AD are Aβ40 and Aβ42, the latter being more toxic and prone to form oligomers. Here, we took a systems biology approach to study two humanized yeast AD models which expressed either Aβ40 or Aβ42 in bioreactor cultures. Strict control of oxygen availability and culture pH, strongly affected chronological lifespan and reduced variations during cell growth...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28796507/molecular-dynamics-study-to-investigate-the-dimeric-structure-of-the-full-length-%C3%AE-synuclein-in-aqueous-solution
#12
Tingting Zhang, Yuanxin Tian, Zhonghuang Li, Siming Liu, Xiang Hu, Zichao Yang, Xiaotong Ling, Shu-Wen Liu, Jiajie Zhang
The mechanisms of dimerization of α-Synuclein from full-length monomers and the structural features have been investigated through molecular dynamics simulations in this study. The dimerization of α-Syn plays a critical role in the fibrillogenesis mechanism and could initiate and trigger α-Syn to aggregate by conformational transforming. According to the alignment between three regions of α-Syn monomer, 8 diverse starting structures have been constructed. However, only 5 configurations show the dimeric structures and the detailed properties of 3 dimers of them are discussed...
August 10, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28796251/differential-spatial-expression-of-peripheral-olfactory-neuron-derived-bace1-induces-olfactory-impairment-by-region-specific-accumulation-of-%C3%AE-amyloid-oligomer
#13
Seung-Jun Yoo, Ji-Hye Lee, So Yeun Kim, Gowoon Son, Jae Yeon Kim, Bongki Cho, Seong-Woon Yu, Keun-A Chang, Yoo-Hun Suh, Cheil Moon
Olfactory dysfunction is a common symptom associated with neurodegenerative diseases including Alzheimer's disease (AD). Although evidence exists to suggest that peripheral olfactory organs are involved in the olfactory dysfunction that accompanies AD pathology, the underlying mechanisms are not fully understood. As confirmed using behavioral tests, transgenic mice overexpressing a Swedish mutant form of human amyloid precursor proteins exhibited olfactory impairments prior to evidence of cognitive impairment...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28795459/dissecting-the-behaviour-of-%C3%AE-amyloid-peptide-variants-during-oligomerization-and-fibrillation
#14
Jing-Ming Shi, Lin Zhang, En-Qi Liu
The oligomerization and fibrillation of β-amyloid (Aβ) peptides are important events in the pathogenesis of Alzheimer's disease. However, the motifs within the Aβ sequence that contribute to oligomerization and fibrillation and the complex interplay among these short motifs are unclear. In this study, the oligomerization and fibrillation abilities of the Aβ variants Aβ1-28, Aβ1-36, Aβ11-42, Aβ17-42, Aβ1-40 and Aβ1-42 were examined by thioflavin T fluorescence, western blotting and transmission electron microscopy...
August 10, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28794261/neuroprotective-astrocyte-derived-insulin-igf-1-stimulate-endocytic-processing-and-extracellular-release-of-neuron-bound-a%C3%AE-oligomers
#15
Jason Pitt, Kyle C Wilcox, Vanessa Tortelli, Luan Pereira Diniz, Maira S Oliveira, Cassandra Dobbins, Xiao-Wen Yu, Sathwik Nandamuri, Flávia C A Gomes, Nadia DiNunno, Kirsten L Viola, Fernanda G De Felice, Sergio T Ferreira, William L Klein
Synaptopathy underlying memory deficits in Alzheimer's disease (AD) is increasingly thought to be instigated by toxic oligomers of the amyloid beta peptide (AβOs). Given the long latency and incomplete penetrance of AD dementia with respect to Aβ pathology, we hypothesized that factors present in the CNS may physiologically protect neurons from the deleterious impact of AβOs. Here we employed physically-separated neuron-astrocyte co-cultures to investigate potential non cell-autonomous neuroprotective factors influencing AβO toxicity...
August 9, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28792099/bead-level-characterization-of-early-stage-amyloid-%C3%AE-42-aggregates-nuclei-and-ionic-concentration-effects
#16
Dingkun Hu, Wei Zhao, Yong Zhu, Hongqi Ai, Baotao Kang
A growing body of evidence shows that soluble Aβ aggregates, oligomers and even protofibrils, may be more neurotoxic than fibrils. Here we employ coarse grain model to investigate the aggregation of 75mer Aβ42 oligomers and salt effect, the cornerstone of fibril evolution. We find that the oligomer morphologies generated by 75 monomers or mixed by both 50 monomers and 5 preset pentameric nuclei are different (spherical vs bar-/disk-shaped) and characterize full of coil content (former) and >70% β-turn one (latter), respectively, indicating a novel role of the nuclei played in the early aggregation stage...
August 9, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28790888/amyloid-%C3%AE-1-42-a%C3%AE-1-42-induces-the-cdk2-mediated-phosphorylation-of-tau-through-the-activation-of-the-mtorc1-signaling-pathway-while-promoting-neuronal-cell-death
#17
Ki Hoon Lee, Sei-Jung Lee, Hyun Jik Lee, Gee Euhn Choi, Young Hyun Jung, Dah Ihm Kim, Amr Ahmed Gabr, Jung Min Ryu, Ho Jae Han
Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by cognitive impairment and memory loss. Amyloid β1-42 (Aβ) and hyper-phosphorylation of microtubule-associated protein tau have been considered as major histological features in AD. However, the mechanism of how Aβ induces the hyper-phosphorylation of tau remains to be clarified. In the present study, we investigated the underlying cellular mechanisms of Aβ with regard to the cell cycle regulatory protein-mediated phosphorylation of tau in promoting neuronal cell death...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28776187/alzheimer-s-disease-related-amyloid-%C3%AE-1-42-peptide-induces-the-loss-of-human-sperm-function
#18
R S Tavares, S Martins, T Almeida-Santos, A P Sousa, J Ramalho-Santos, O A da Cruz E Silva
Characteristically identified as the main component of senile plaques present in patients suffering from Alzheimer's disease, Aβ has been detected in human testis and reproductive fluids, but its effect on spermatozoa has not been addressed. The present study evaluated whether the most toxic and aggregant amyloid precursor protein (APP)-proteolytic product, amyloid-β1-42 (Aβ1-42), was capable of affecting sperm functionality. Normozoospermic samples were either exposed to different Aβ1-42 doses or to the untreated and scrambled controls for a maximum of 48 h at 37 °C and 5%CO2, and motility, viability and mitochondrial status were evaluated...
August 3, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28768117/cationic-surfactant-mediated-fibrillogenesis-in-bovine-liver-catalase-a-biophysical-approach
#19
MohsinVahid Khan, Masihuz Zaman, TajalliIlm Chandel, Mohammad Khursheed Siddiqui, Mohd Rehan Ajmal, Ali Saber Abdelhameed, RizwanHasan Khan
Protein aggregation into oligomers and mature fibrils are associated with more than 20 diseases in humans. The interactions between cationic surfactants dodecyltrimethylammonium bromide (DTAB) andtetradecyltrimethylammonium bromide (TTAB) with varying alkyl chain lengths and bovine liver catalase (BLC) were examined by various biophysical approaches. The delicate coordination of electrostatic and hydrophobic interactions with protein, play imperative role in aggregation. In this article we have reconnoitered the relation between charge, hydrophobicity and cationic surfactants DTAB and TTAB on BLC at pH 7...
August 2, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28760925/the-cholesterol-ester-cycle-regulates-signalling-complexes-and-synapse-damage-caused-by-amyloid-%C3%AE
#20
Ewan West, Craig Osborne, Clive Bate
Cholesterol is required for the formation and function of some signalling platforms. In synaptosomes amyloid-β (Aβ) oligomers, the causative agent in Alzheimer's disease, bind to cellular prion proteins (PrP(C)) resulting in increased cholesterol concentrations, translocation of cytoplasmic phospholipase A2 (cPLA2) to lipid rafts and activation of cPLA2 The formation of Aβ:PrP(C) complexes was controlled by the cholesterol ester cycle. Aβ activated cholesterol ester hydrolases which released cholesterol from stores of cholesterol esters and stabilised Aβ:PrP(C) complexes resulting in activated cPLA2 Conversely, cholesterol esterification reduced cholesterol concentrations causing the dispersal of Aβ:PrP(C) complexes...
July 31, 2017: Journal of Cell Science
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