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https://www.readbyqxmd.com/read/29786756/backbone-nmr-assignments-of-hypf-n-under-conditions-generating-toxic-and-non-toxic-oligomers
#1
Jayneil R Patel, Yingqi Xu, Claudia Capitini, Fabrizio Chiti, Alfonso De Simone
The HypF protein is involved in the maturation and regulation of hydrogenases. The N-terminal domain of HypF (HypF-N) has served as a key model system to study the pathways of protein amyloid formation and the nature of the toxicity of pre-fibrilar protein oligomers. This domain can aggregate into two forms of oligomers having significantly different toxic effects when added to neuronal cultures. Here, NMR assignments of HypF-N backbone resonances are presented in its native state and under the conditions favouring the formation of toxic and non-toxic oligomers...
May 21, 2018: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/29786737/anti-amyloidogenic-properties-of-an-ethyl-acetate-fraction-from-actinidia-arguta-in-a%C3%AE-1-42-induced-icr-mice
#2
Jeong Su Ha, Jong Min Kim, Seon Kyeong Park, Jin Yong Kang, Du Sang Lee, Uk Lee, Dae-Ok Kim, Sung-Gil Choi, Ho Jin Heo
This study aimed to investigate the ameliorating effect of an ethyl acetate fraction from the fruit Actinidia arguta (EFAA) on amyloid beta (Aβ)-induced neurotoxicity and cognitive deficits in ICR mice. EFAA showed potent protective effects against Aβ-induced neurotoxicity through 2',7'-dichlorofluorescein diacetate (DCF-DA), 2',3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release into the assay medium. EFAA treatment reduced the intracellular ROS level and lactate dehydrogenase (LDH) release in the mitochondria, and increased cell viability in Aβ-induced neuroblastoma MC-IXC cells...
May 22, 2018: Food & Function
https://www.readbyqxmd.com/read/29786594/-brain-microbleeds-definition-pathophysiology-and-the-consequences
#3
Marek Mazurek, Ewa Papuć, Konrad Rejdak
Brain microbleeds are defined as small, circular hypointense changes in T2-sequensec of brain MRI, well demarcated from the surrounding tissue. They represent the phagocytized products of blood distribution extravasated from pathologically altered vessels. The echo-T2-dependent gradient (GRE) and magnetic susceptibility testing (SWI) sequences are usually used to visualize them. The pathogenesis of microbleeds very complex but angiopathy associated with arterial hypertension and cerebral amyloid angiopathy play a special role...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29786080/atomic-structures-of-tdp-43-lcd-segments-and-insights-into-reversible-or-pathogenic-aggregation
#4
Elizabeth L Guenther, Qin Cao, Hamilton Trinh, Jiahui Lu, Michael R Sawaya, Duilio Cascio, David R Boyer, Jose A Rodriguez, Michael P Hughes, David S Eisenberg
The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules...
May 21, 2018: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29784771/prion-replication-in-the-mammalian-cytosol-functional-regions-within-a-prion-domain-driving-induction-propagation-and-inheritance
#5
Yvonne Duernberger, Shu Liu, Katrin Riemschoss, Lydia Paulsen, Romina Bester, Peer-Hendrik Kuhn, Manuel Schölling, Stefan F Lichtenthaler, Ina Vorberg
Prions of lower eukaryotes are transmissible protein particles that propagate by converting homotypic soluble proteins into growing protein assemblies. Prion activity is conferred by so-called prion domains, regions of low complexity that are often enriched in glutamines and asparagines (Q/N). The compositional similarity of fungal prion domains with intrinsically disordered domains found in many mammalian proteins raises the question if similar sequence elements can drive prion-like phenomena in mammals. Here we define sequence features of the prototype S...
May 21, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29784055/usefulness-of-c-reactive-protein-and-serum-amyloid-a-in-early-detection-of-postoperative-infectious-complications-to-tibial-plateau-leveling-osteotomy-in-dogs
#6
Karin Löfqvist, Mads Kjelgaard-Hansen, Michelle Brønniche Møller Nielsen
BACKGROUND: Cranial cruciate ligament rupture is a prevalent injury in dogs, and tibial plateau leveling osteotomy (TPLO) is one of the preferred surgical techniques. Surgical site infection is a possible complication following TPLO and measurement of serum acute phase proteins is suggested to be a way to early recognize and distinguish postoperative infectious complications from normal postoperative inflammatory conditions. In this study we investigate the changes in concentrations of the systemic inflammatory markers C-reactive protein (CRP) and serum amyloid A (SAA) following tibial plateau leveling osteotomy (TPLO) in dogs and evaluate if deviations from the changes expectedly induced by the surgical procedure are useful in early detection of post-surgical infections...
May 21, 2018: Acta Veterinaria Scandinavica
https://www.readbyqxmd.com/read/29784049/identification-and-therapeutic-modulation-of-a-pro-inflammatory-subset-of-disease-associated-microglia-in-alzheimer-s-disease
#7
Srikant Rangaraju, Eric B Dammer, Syed Ali Raza, Priyadharshini Rathakrishnan, Hailian Xiao, Tianwen Gao, Duc M Duong, Michael W Pennington, James J Lah, Nicholas T Seyfried, Allan I Levey
BACKGROUND: Disease-associated-microglia (DAM) represent transcriptionally-distinct and neurodegeneration-specific microglial profiles with unclear significance in Alzheimer's disease (AD). An understanding of heterogeneity within DAM and their key regulators may guide pre-clinical experimentation and drug discovery. METHODS: Weighted co-expression network analysis (WGCNA) was applied to existing microglial transcriptomic datasets from neuroinflammatory and neurodegenerative disease mouse models to identify modules of highly co-expressed genes...
May 21, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29783682/heat-shock-gene-inactivation-and-protein-aggregation-with-links-to-chronic-diseases
#8
Ian James Martins
The heat shock response involved in protein misfolding is linked to the formation of toxic immunogenic proteins with heat shock proteins (HSP) as regulators of amyloid beta aggregation. The defective amyloid beta trafficking between different intracellular compartments is now relevant to HSPs and autoimmunity. Overnutrition, temperature dysregulation, and stress repress the heat shock gene Sirtuin 1 with the induction of HSP regulated amyloid beta aggregation involved in the autoimmune response. Defective circadian rhythm alterations are connected to inactivation of the peripheral sink amyloid beta clearance pathway and related to insulin resistance, protein aggregation, and autoimmune disease in non-alcoholic fatty liver disease (NAFLD) and various neurodegenerative diseases such as Alzheimer's disease...
May 18, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29782959/targeting-central-%C3%AE-2-receptors-ameliorates-streptozotocin-induced-neuroinflammation-via-inhibition-of-glycogen-synthase-kinase3-pathway-in-mice
#9
Nora O Abdel Rasheed, Nesrine S El-Sayed, Aiman S El-Khatib
Alzheimer's disease (AD) is portrayed by progressive cognitive decline and pathological deposition of amyloid plaques as well as neurofibrillary tangles. Most of AD cases are sporadic, resulting from overlap of various environmental and genetic factors. Intra-cerebroventricular injection of streptozotocin (STZ) leads to insulin resistance brain state accompanied by memory decline, oxidative stress, and neuro-degeneration which mimic the pathologies associated with sporadic Alzheimer's disease (SAD). In the current study, protective effects of formoterol in STZ-induced SAD were studied...
May 18, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29782912/in-vitro-protective-activity-of-south-australian-marine-sponge-and-macroalgae-extracts-against-amyloid-beta-a%C3%AE-1-42-induced-neurotoxicity-in-pc-12-cells
#10
Mousa Alghazwi, Scott Smid, Wei Zhang
South Australia is a biodiversity hotspot of marine sponges and macroalgae. This study aimed to evaluate the potential neuroprotective activity of extracts from these two marine sources by reducing the toxicity of human amyloid beta Aβ1-42 in a cell model assay using PC-12 cells. A total of 92 extracts (43, 13, 16, and 20 extracts from sponge of 8 orders and 17 families, green algae of 3 orders and 4 families, brown algae of 6 orders and 8 families, and red algae of 5 orders and 10 families, respectively) were initially screened at three different concentrations (0...
May 18, 2018: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/29782911/estrogen-deficiency-exacerbates-a%C3%AE-induced-memory-impairment-through-enhancement-of-neuroinflammation-amylodogenesis-and-nf-%C3%A4-b-activation-in-ovariectomized-mice
#11
Jaesuk Yun, In Jun Yeo, Chul Ju Hwang, Dong-Young Choi, Hyung-Sik Im, Ji Youg Kim, Won Rak Choi, Myung Hee Jung, Sang-Bae Han, Jin Tae Hong
Estrogen is well known to have a preventative effect in Alzheimer's disease (AD) pathology. Several studies have demonstrated that nuclear factor kappa-B (NF-ĸB) can contribute to the effects of estrogen on the development of AD. We investigated whether NF-ĸB affects amyloid-beta (Aβ)-induced memory impairment in an estrogen-lacking condition. In the present study, nine-week-old Institute cancer research (ICR) mice were ovariectomized to block estrogen stimulation. Ten weeks after the ovariectomization, mice were administered with Aβ (300 pmol) via intracerebroventricular (ICV) infusion for 2 weeks...
May 18, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29782905/pathology-of-nnos-expressing-gabaergic-neurons-in-mouse-model-of-alzheimer-s-disease
#12
Seungho Choi, Je-Seong Won, Steven L Carroll, Balasubramaniam Annamalai, Inderjit Singh, Avtar K Singh
Alzheimer's disease (AD) is the most common form of dementia that is often accompanied by mood and emotional disturbances and seizures. There is growing body of evidence that neurons expressing γ-aminobutyric acid (GABA) play an important role in regulation of cognition, mood, and emotion as well as seizure susceptibility, but participation of GABAergic neuronal pathology in Alzheimer's disease (AD) is not understood well at present. Here, we report that transgenic mice expressing human amyloid precursor protein Swedish-Deutch-Iowa mutant (APPSweDI ) exhibit early loss of neurons expressing GAD67, a GABA synthesizing enzyme, in advance to the loss of pyramidal neurons in hippocampal CA1 region...
May 18, 2018: Neuroscience
https://www.readbyqxmd.com/read/29782835/multi-pronged-interactions-underlie-inhibition-of-%C3%AE-synuclein-aggregation-by-%C3%AE-synuclein
#13
Jonathan K Williams, Xue Yang, Tamr B Atieh, Michael P Olson, Sagar D Khare, Jean Baum
The intrinsically disordered protein β-synuclein is known to inhibit the aggregation of its intrinsically disordered homolog, α-synuclein, which is implicated in Parkinson's disease. While β-synuclein itself does not form fibrils at the cytoplasmic pH7.4, alteration of pH and other environmental perturbations are known to induce its fibrilization. However, the sequence and structural determinants of β-synuclein inhibition and self-aggregation are not well understood. We have utilized a series of domain-swapped chimeras of α-synuclein and β-synuclein to probe the relative contributions of the N-terminal, C-terminal and the central Non-Amyloid-β Component (NAC) domains to the inhibition of α-synuclein aggregation...
May 18, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29782833/insights-into-stabilizing-forces-in-amyloid-fibrils-of-differing-sizes-from-polarizable-molecular-dynamics-simulations
#14
Darcy S Davidson, Anne M Brown, Justin A Lemkul
Pathological aggregation of amyloid-forming proteins is a hallmark of a number of human diseases, including Alzheimer's, type 2 diabetes, Parkinson's, and more. Despite having very different primary amino acid sequences, these amyloid proteins form similar supramolecular, fibril structures that are highly resilient to physical and chemical denaturation. To better understand the structural stability of disease-related amyloids and to gain a greater understanding of factors that stabilize functional amyloid assemblies, insights into tertiary and quaternary interactions are needed...
May 18, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29782798/regulatory-activities-of-dopamine-and-its-derivatives-towards-metal-free-and-metal-induced-amyloid-%C3%AE-aggregation-oxidative-stress-and-inflammation-in-alzheimer-s-disease
#15
Eunju Nam, Jeffrey S Derrick, Seunghee Lee, Juhye Kang, Jiyeon Han, Shin Jung C Lee, Su Wol Chung, Mi Hee Lim
A catecholamine neurotransmitter, dopamine (DA), is suggested to be linked to the pathology of dementia; however, the involvement of DA and its structural analogues in the pathogenesis of Alzheimer's disease (AD), the most common form of dementia, composed of multiple pathogenic factors has not been clear. Herein, we report that DA and its rationally designed structural derivatives (1-6) based on DA's oxidative transformation are able to modulate multiple pathological elements found in AD [ i.e., metal ions, metal-free amyloid-β (Aβ), metal-bound Aβ (metal-Aβ), and reactive oxygen species (ROS)], with demonstration of detailed molecular-level mechanisms...
May 21, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29782794/peptides-peptidomimetics-and-carbohydrate-peptide-conjugates-as-amyloidogenic-aggregation-inhibitors-for-alzheimer-s-disease
#16
Philip Ryan, Bhautikkumar Patel, Vivek Makwana, Hemant Jadhav, Milton John Kiefel, Andrew Davey, Tristan Reekie, Santosh Rudrawar, Michael Kassiou
Alzheimer's disease (AD) is a progressive neurodegenerative disorder accounting for 60-80% of dementia cases. For many years, AD causality was attributed to amyloid-β (Aβ) aggregated species. Recently, multiple therapies that target Aβ aggregation have failed in clinical trials, since Aβ aggregation is found in AD and healthy patients. Attention has therefore shifted towards the aggregation of the peptide tau as a major driver of AD. Numerous inhibitors of tau-based pathology have recently been developed...
May 21, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29782502/a-monoclonal-antibody-targeting-amyloid-%C3%AE-a%C3%AE-restores-complement-factor-i-bioactivity-potential-implications-in-age-related-macular-degeneration-and-alzheimer-s-disease
#17
Kameran Lashkari, Gianna Teague, Hong Chen, Yong-Qing Lin, Sanjay Kumar, Megan M McLaughlin, Francisco J López
Activation of the alternative complement cascade has been implicated in the pathogenesis of age related macular degeneration (AMD) and Alzheimer's disease (AD). Amyloid β (Aβ), a component of drusen, may promote complement activation by inhibiting CFI bioactivity. We determined whether Aβ reduced CFI bioactivity and whether antibodies against Aβ including a monoclonal antibody, GSK933776 could restore CFI bioactivity. We also measured CFI bioactivity in plasma of subjects with AMD and AD. In support of the GSK933776 development program in AMD (geographic atrophy), we developed a quantitative assay to measure CFI bioactivity based on its ability to cleave C3b to iC3b, and repeated it in presence or absence of Aβ and anti-Aβ antibodies...
2018: PloS One
https://www.readbyqxmd.com/read/29782318/amyloid-accumulation-and-cognitive-decline-in-clinically-normal-older-individuals-implications-for-aging-and-early-alzheimer-s-disease
#18
Elizabeth C Mormino, Kathryn V Papp
 The aberrant accumulation of the amyloid protein is a critical and early event in the Alzheimer's disease (AD) cascade. Given the early involvement of this pathological process, it is not surprising that many clinically normal (CN) older individuals demonstrate evidence of abnormal Aβ at postmortem examination and in vivo using either CSF or PET imaging. Converging evidence across multiple research groups suggests that the presence of abnormal Aβ among CN individuals is associated with elevated risk of future clinical impairment and cognitive decline...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29782317/dementia-research-populations-progress-problems-and-predictions
#19
Sally Hunter, Nadja Smailagic, Carol Brayne
Alzheimer's disease (AD) is a clinicopathologically defined syndrome leading to cognitive impairment. Following the recent failures of amyloid-based randomized controlled trials to change the course of AD, there are growing calls for a re-evaluation of basic AD research. Epidemiology offers one approach to integrating the available evidence. Here we examine relationships between evidence from population-based, clinicopathological studies of brain aging and a range of hypotheses from all areas of AD research...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29782315/tlr4-gene-expression-and-pro-inflammatory-cytokines-in-alzheimer-s-disease-and-in-response-to-hippocampal-deafferentation-in-rodents
#20
Justin Miron, Cynthia Picard, Josée Frappier, Doris Dea, Louise Théroux, Judes Poirier
One important aspect in Alzheimer's disease pathology is the presence of chronic inflammation. Considering its role as a key receptor in the microglial innate immune system, TLR4 was shown to regulate the binding and phagocytosis of amyloid plaques by microglia in several mouse models of amyloidosis, as well as the production of pro-inflammatory cytokines. To our knowledge, TLR4 and its association with cytokines have not been thoroughly examined in the brains of subjects affected with Alzheimer's disease. Using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in postmortem human brains, we observed increased expression for the TLR4 and TNF genes (p = 0...
May 16, 2018: Journal of Alzheimer's Disease: JAD
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