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amyloid oligomer

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https://www.readbyqxmd.com/read/28211900/amyloid-%C3%AE-oligomers-interact-with-neurexin-and-diminish-neurexin-mediated-excitatory-presynaptic-organization
#1
Yusuke Naito, Yuko Tanabe, Alfred Kihoon Lee, Edith Hamel, Hideto Takahashi
Alzheimer's disease (AD) is characterized by excessive production and deposition of amyloid-beta (Aβ) proteins as well as synapse dysfunction and loss. While soluble Aβ oligomers (AβOs) have deleterious effects on synapse function and reduce synapse number, the underlying molecular mechanisms are not well understood. Here we screened synaptic organizer proteins for cell-surface interaction with AβOs and identified a novel interaction between neurexins (NRXs) and AβOs. AβOs bind to NRXs via the N-terminal histidine-rich domain (HRD) of β-NRX1/2/3 and alternatively-spliced inserts at splicing site 4 of NRX1/2...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211253/comparison-of-neurotoxicity-of-different-aggregated-forms-of-a%C3%AE-40-a%C3%AE-42-and-a%C3%AE-43-in-cell-cultures
#2
Lu Fu, Yao Sun, Yongqing Guo, Yan Chen, Bin Yu, Haihong Zhang, Jiaxin Wu, Xianghui Yu, Wei Kong, Hui Wu
The abnormal deposition of amyloid-β (Aβ) peptides in the brain is the main neuropathological hallmark of Alzheimer's disease (AD). Amyloid deposits are formed by a heterogeneous mixture of Aβ peptides, among which the most studied are Aβ40 and Aβ42. Aβ40 is abundantly produced in the human brain, but the level of Aβ42 is remarkably increased in the brain of AD patients. Aside from Aβ40 and Aβ42, recent data have raised the possibility that Aβ43 peptides may be instrumental in AD pathogenesis. Besides its length, whether the Aβ aggregated form accounts for the neurotoxicity is also particularly controversial...
February 16, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28211008/injected-amyloid-beta-in-the-olfactory-bulb-transfers-to-other-brain-regions-via-neural-connections-in-mice
#3
Baixuan He, Minying Zheng, Qiang Liu, Zhe Shi, Simei Long, Xilin Lu, Zhong Pei, Ti-Fei Yuan, Huanxing Su, Xiaoli Yao
Alzheimer's disease (AD) is characterized by progressive neuronal degeneration and pathological accumulation of amyloid plaques in the brain. It has been proposed that the prion-like spreading of amyloid beta (Aβ) protein could contribute to the progression of the disease. Olfactory bulb (OB) is one of the earliest brain regions affected in AD and olfaction is easily impaired prior to cognitive symptoms. However, it remains unclear whether Aβ accumulation in the OB would spread along olfactory projections to other connected brain regions and trigger further neurodegeneration...
February 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28197669/clearance-of-cerebral-a%C3%AE-in-alzheimer-s-disease-reassessing-the-role-of-microglia-and-monocytes
#4
REVIEW
Leah Zuroff, David Daley, Keith L Black, Maya Koronyo-Hamaoui
Deficiency in cerebral amyloid β-protein (Aβ) clearance is implicated in the pathogenesis of the common late-onset forms of Alzheimer's disease (AD). Accumulation of misfolded Aβ in the brain is believed to be a net result of imbalance between its production and removal. This in turn may trigger neuroinflammation, progressive synaptic loss, and ultimately cognitive decline. Clearance of cerebral Aβ is a complex process mediated by various systems and cell types, including vascular transport across the blood-brain barrier, glymphatic drainage, and engulfment and degradation by resident microglia and infiltrating innate immune cells...
February 14, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28195470/total-synthesis-confirms-the-molecular-structure-proposed-for-oxidized-levuglandin-d2
#5
Yu-Shiuan Cheng, Wenyuan Yu, Yunfeng Xu, Robert G Salomon
Levuglandins (LG)D2 and LGE2 are γ-ketoaldehyde levulinaldehyde derivatives with prostanoid side chains produced by spontaneous rearrangement of the endoperoxide intermediate PGH2 in the biosynthesis of prostaglandins. Covalent adduction of LGs with the amyloid peptide Aβ1-42 promotes formation of the type of oligomers that have been associated with neurotoxicity and are a pathologic hallmark of Alzheimer's disease. Within 1 min of their generation during the production of PGH2 by cyclooxygenation of arachidonic acid, LGs are sequestered by covalent adduction to proteins...
February 14, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28193356/multivalent-foldamer-based-affinity-assay-for-selective-recognition-of-a%C3%AE-oligomers
#6
Gábor Olajos, Éva Bartus, Ildikó Schuster, Gergely Lautner, Róbert E Gyurcsányi, Titanilla Szögi, Lívia Fülöp, Tamás A Martinek
Mimicking the molecular recognition functionality of antibodies is a great challenge. Foldamers are attractive candidates because of their relatively small size and designable interaction surface. This paper describes a sandwich type enzyme-linked immunoassay with a tetravalent β-peptide foldamer helix array as capture element and enzyme labeled tracer antibodies. The assay was found to be selective to β-amyloid oligomeric species with surface features transiently present in ongoing aggregation. In optimized conditions, with special emphasis on the foldamer immobilization, a detection limit of 5 pM was achieved with a linear range of 10-500 pM...
April 1, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28186729/n-terminal-hypothesis-for-alzheimer-s-disease
#7
Brian Murray, Bhanushee Sharma, Georges Belfort
Although the amyloid (abeta peptide, Aβ) hypothesis is 25 years old, is the dominant model of Alzheimer's disease (AD) pathogenesis, and guides the development of potential treatments, it is still controversial. One possible reason is a lack of a mechanistic path from the cleavage products of the amyloid precursor protein (APP) such as soluble Aβ monomer and soluble molecular fragments to the deleterious effects on synaptic form and function. From a review of the recent literature and our own published work including aggregation kinetics and structural morphology, Aβ clearance, molecular simulations, long-term potentiation measurements with inhibition binding, and the binding of a commercial monoclonal antibody, aducanumab, we hypothesize that the N-terminal domains of neurotoxic Aβ oligomers are implicated in causing the disease...
February 10, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28183246/solid-state-structure-of-abeta-ab-in-alzheimer-s-disease
#8
Junxia Lu, Xing-Qi Dong, Jian-Jun Zhang
Alzheimer's disease (AD) has become the most common neurodegenerative disease. The deposition of amyloid fibrils in the brain is one of the characteristics of AD. The fibrils are composed of amyloid-b peptide (Ab). Ab is produced through a series event of protease cleavage of a transmembrane protein called β-amyloid precursor protein (APP) which is commonly expressed in the brain. The production of Ab and its propensity to aggregation to form oligomers and fibrils are believed to initiate a sequence of events that lead to AD dementia...
February 8, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28170248/analyzing-amyloid-beta-aggregates-with-a-combinatorial-fluorescent-molecular-sensor
#9
Joydev Hatai, Leila Motiei, David Margulies
Different amyloid beta (Aβ) aggregates can be discriminated by a combinatorial fluorescent molecular sensor. The unique optical fingerprints generated by the unimolecular analytical device provide a simple means to differentiate among aggregates generated from different alloforms or through distinct pathways. The sensor has also been used to track dynamic changes that occur in Aβ aggregation states, which result from the formation of low molecular weight oligomers, high molecular weight oligomers, protofibrils, and fibrils...
February 7, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28162045/scrutiny-of-the-mechanism-of-small-molecule-inhibitor-preventing-conformational-transition-of-amyloid-%C3%AE-42-monomer-insights-from-molecular-dynamics-simulations
#10
Suniba Shuaib, Bhupesh Goyal
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by loss of intellectual functioning of brain and memory loss. According to amyloid cascade hypothesis, aggregation of amyloid-β42 (Aβ42) peptide can generate toxic oligomers and their accumulation in the brain is responsible for the onset of AD. In spite of carrying out a large number of experimental studies on inhibition of Aβ42 aggregation by small molecules, the detailed inhibitory mechanism remains elusive. In the present study, comparable molecular dynamics (MD) simulations were performed to elucidate the inhibitory mechanism of a sulfonamide inhibitor C1 (2,5-dichloro-N-(4-piperidinophenyl)-3-thiophenesulfonamide), reported for its in vitro and in vivo anti-aggregation activity against Aβ42...
February 6, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28155597/astrocytic-expression-of-the-immunoreceptor-cd300f-protects-hippocampal-neurons-from-amyloid-%C3%AE-oligomer-toxicity-in-vitro
#11
Thiago Zaqueu Lima, Luis Roberto Sardinha, Joan Sayós, Luiz Eugênio Mello, Hugo Peluffo
BACKGROUND: Astrocytes contribute to neuroinflammation that accompanies neurodegenerative disorders such as Alzheimer's disease (AD). In this sense, the toxicity of these diseases might be attenuated through the modulation of astrocytic inflammatory responses. Recently, the CD300f immunoreceptor was described as a new member of the CD300 immunoreceptor family, showing promising modulatory properties. OBJECTIVE: Here, we investigated whether overexpression of hCD300f (the human isoform of CD300f) in astrocytes protects hippocampal neurons against the degeneration induced by amyloid-beta (Aβ) oligomer...
2, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28154182/reduced-lipid-bilayer-thickness-regulates-the-aggregation-and-cytotoxicity-of-amyloid-%C3%AE
#12
Kyle J Korshavn, Cristina Satriano, Yuxi Lin, Rongchun Zhang, Mark Dulchavsky, Anirban Bhunia, Magdalena I Ivanova, Young-Ho Lee, Carmelo La Rosa, Mi Hee Lim, Ayyalusamy Ramamoorthy
The aggregation of amyloid-Aβ (Aβ) on lipid bilayers has been implicated as a mechanism by which Aβ exerts its toxicity in Alzheimer's disease (AD). Lipid bilayer thinning has been observed during both oxidative stress and protein aggregation in AD, but whether these pathological modifications of the bilayer correlate with Aβ misfolding is unclear. Here, we studied peptide-lipid interactions in synthetic bilayers of the short-chain lipid dilauroyl phosphatidylcholine (DLPC) as a simplified model for diseased bilayers to determine their impact on Aβ aggregate, protofibril, and fibril formation...
February 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28153323/in-vitro-monitoring-of-amyloid-%C3%AE-peptide-oligomerization-by-electrospray-differential-mobility-analysis-an-alternative-tool-to-evaluate-alzheimer-s-disease-drug-candidates
#13
Dimitri Brinet, François Gaie-Levrel, Vincent Delatour, Julia Kaffy, Sandrine Ongeri, Myriam Taverna
Alzheimer's disease (AD) is a neurodegenerative disorder linked to protein aggregation, like more than twenty other human pathologies. One major protein incriminated in AD is the 42-residue amyloid-β peptide (Aβ1-42) which aggregates to form neurotoxic oligomers and fibrils. While, low molecular weight oligomers have been evidenced as neurotoxic species, only scarce methods raise the challenge to monitor the beginning of the aggregation process, called oligomerization. We propose here an innovative and fast monitoring of the time-dependent Aβ1-42 oligomerization pattern by electrospray differential mobility analysis (ES-DMA)...
April 1, 2017: Talanta
https://www.readbyqxmd.com/read/28147245/angiotensin-1-7-administration-attenuates-alzheimer-s-disease-like-neuropathology-in-rats-with-streptozotocin-induced-diabetes-via-mas-receptor-activation
#14
Jin-Liang Chen, Dong-Ling Zhang, Yue Sun, Yu-Xing Zhao, Ke-Xiang Zhao, Die Pu, Qian Xiao
Diabetes mellitus (DM) is associated with cognitive deficits and an increased risk of Alzheimer's disease (AD). Recently, a newly identified heptapeptide of the renin-angiotensin system (RAS), angiotensin-(1-7) [Ang-(1-7)], was found to protect against brain damage. This study investigated the effects of Ang-(1-7) on diabetes-induced cognitive deficits. Sprague-Dawley rats were randomly divided into four groups. Diabetes was induced via single i.p. streptozotocin (STZ) injections. Ten weeks after diabetes induction, rats in each group received an intracerebral-ventricular (ICV) infusion of either vehicle, Ang-(1-7) alone, or Ang-(1-7)+A779 daily for two weeks...
January 29, 2017: Neuroscience
https://www.readbyqxmd.com/read/28143556/aging-and-amyloid-%C3%AE-oligomers-enhance-tlr4-expression-lps-induced-ca-2-responses-and-neuron-cell-death-in-cultured-rat-hippocampal-neurons
#15
María Calvo-Rodríguez, Carmen de la Fuente, Mónica García-Durillo, Carmen García-Rodríguez, Carlos Villalobos, Lucía Núñez
BACKGROUND: Toll-like receptors (TLRs) are transmembrane pattern-recognition receptors of the innate immune system recognizing diverse pathogen-derived and tissue damage-related ligands. It has been suggested that TLR signaling contributes to the pathogenesis of age-related, neurodegenerative diseases, including Alzheimer's disease (AD). AD is associated to oligomers of the amyloid β peptide (Aβo) that cause intracellular Ca(2+) dishomeostasis and neuron cell death in rat hippocampal neurons...
January 31, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28140589/stereoisomers-probe-steric-zippers-in-amyloid-%C3%AE
#16
Bappaditya Chandra, Alexander Korn, Barun Kumar Maity, Juliane Adler, Anoop Rawat, Martin Krueger, Daniel Huster, Sudipta Maiti
Shape complementarity between close-packed residues plays a critical role in the amyloid aggregation process. Here, we probe such "steric zipper" interactions in amyloid-β (Aβ40), whose aggregation is linked to Alzheimer's disease, by replacing natural residues by their stereoisomers. Such mutations are expected to specifically destabilize the shape sensitive "packing" interactions, which may potentially increase their solubility and change other properties. We study the stereomutants DF19 and DL34 and also the DA2/DF4/DH6/DS8 mutant of Aβ40...
February 14, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28140404/particulate-air-pollutants-apoe-alleles-and-their-contributions-to-cognitive-impairment-in-older-women-and-to-amyloidogenesis-in-experimental-models
#17
M Cacciottolo, X Wang, I Driscoll, N Woodward, A Saffari, J Reyes, M L Serre, W Vizuete, C Sioutas, T E Morgan, M Gatz, H C Chui, S A Shumaker, S M Resnick, M A Espeland, C E Finch, J C Chen
Exposure to particulate matter (PM) in the ambient air and its interactions with APOE alleles may contribute to the acceleration of brain aging and the pathogenesis of Alzheimer's disease (AD). Neurodegenerative effects of particulate air pollutants were examined in a US-wide cohort of older women from the Women's Health Initiative Memory Study (WHIMS) and in experimental mouse models. Residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE ɛ4/4 carriers...
January 31, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28137266/the-neurotoxicity-of-amyloid-%C3%AE-protein-oligomers-is-reversible-in-a-primary-neuron-model
#18
Daisuke Tanokashira, Naomi Mamada, Fumiko Yamamoto, Kaori Taniguchi, Akira Tamaoka, Madepalli K Lakshmana, Wataru Araki
Alzheimer's disease (AD) is characterized by the accumulation of extracellular amyloid β-protein (Aβ) and intracellular hyperphosphorylated tau proteins. Recent evidence suggests that soluble Aβ oligomers elicit neurotoxicity and synaptotoxicity, including tau abnormalities, and play an initiating role in the development of AD pathology. In this study, we focused on the unclarified issue of whether the neurotoxicity of Aβ oligomers is a reversible process. Using a primary neuron culture model, we examined whether the neurotoxic effects induced by 2-day treatment with Aβ42 oligomers (Aβ-O) are reversible during a subsequent 2-day withdrawal period...
January 31, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28135799/amyloid-%C3%AE-ion-channels-in-a-membrane-comprised-of-brain-total-lipid-extracts
#19
Joon Lee, Young Hun Kim, Fernando Teran Arce, Alan L Gillman, Hyunbum Jang, Bruce L Kagan, Ruth Nussinov, Jerry Yang, Ratnesh Lal
Amyloid-β (Aβ) oligomers are the predominant toxic species in the pathology of Alzheimer's disease. The prevailing mechanism for toxicity by Aβ oligomers includes ionic homeostasis destabilization in neuronal cells by forming ion channels. These channel structures have been previously studied in model lipid bilayers. In order to gain further insight into the interaction of Aβ oligomers with natural membrane compositions, we have examined the structures and conductivities of Aβ oligomers in a membrane composed of brain total lipid extract (BTLE)...
January 30, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28127995/targeting-%C3%AE-amyloid-plaques-and-oligomers-development-of-near-ir-fluorescence-imaging-probes
#20
Hongwu Liu, Jian Yang, Letian Wang, Yungen Xu, Siyuan Zhang, Jie Lv, Chongzhao Ran, Yuyan Li
Evidence indicated that shifting treatment to a presymptomatic stage may produce significant benefits to prevent/alleviate the progression of Alzheimer's disease (AD); in particular, early incorporation of noninvasive imaging and biomarker testing will be significantly beneficial for AD drug development. Based on amyloid cascade hypothesis and its revised version, both β-amyloid deposition and soluble oligomeric species could be good diagnostic biomarkers for AD. Near-IR fluorescence (NIRF) imaging, which so far is limited to animal studies, is a promising method for its incomparable advantages such as low cost, high-throughput and easy operation...
January 27, 2017: Future Medicinal Chemistry
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