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https://www.readbyqxmd.com/read/28651008/production-and-purification-of-human-hsp90%C3%AE-in-escherichia-coli
#1
Martina Radli, Dmitry B Veprintsev, Stefan G D Rüdiger
The molecular chaperone Hsp90 is an essential member of the cellular proteostasis system. It plays an important role in the stabilisation and activation of a large number of client proteins and is involved in fatal disease processes, e.g. Alzheimer disease, cancer and cystic fibrosis. This makes Hsp90 a crucial protein to study. Mechanistic studies require large amounts of protein but the production and purification of recombinant human Hsp90 in Escherichia coli is challenging and laborious. Here we identified conditions that influence Hsp90 production, and optimised a fast and efficient purification protocol...
2017: PloS One
https://www.readbyqxmd.com/read/28650998/functional-annotation-of-alzheimer-s-disease-associated-loci-revealed-by-gwass
#2
Zengpeng Han, Han Huang, Yue Gao, Qingyang Huang
Genome-wide association studies (GWASs) discovered a number of SNPs and genes associated with Alzheimer's disease (AD). However, how these SNPs and genes influence the liability to AD is not fully understood. We deployed computational approaches to explore the function and action mechanisms of AD -related SNPs and genes identified by GWASs, including the effects of 195 GWAS lead SNPs and 338 proxy SNPs on miRNAs binding and protein phosphorylation, their RegulomeDB and 3DSNP scores, and gene ontology, pathway enrichment and protein-protein interaction network of 126 AD-associated genes...
2017: PloS One
https://www.readbyqxmd.com/read/28650994/abnormal-global-functional-network-connectivity-and-its-relationship-to-medial-temporal-atrophy-in-patients-with-amnestic-mild-cognitive-impairment
#3
Can Sheng, Mingrui Xia, Haikuo Yu, Yue Huang, Yan Lu, Fang Liu, Yong He, Ying Han
BACKGROUND: Amnestic mild cognitive impairment (aMCI), which is recently considered as a high risk status for developing Alzheimer's disease (AD), manifests with gray matter atrophy and increased focal functional activity in the medial temporal lobe (MTL). However, the abnormalities of whole-brain functional network connectivity in aMCI and its relationship to medial temporal atrophy (MTA) remain unknown. METHODS: In this study, thirty-six aMCI patients and thirty-five healthy controls (HCs) were recruited...
2017: PloS One
https://www.readbyqxmd.com/read/28650631/effect-of-the-biphenyl-neolignan-honokiol-on-a%C3%AE-42-induced-toxicity-in-caenorhabditis-elegans-a%C3%AE-42-fibrillation-cholinesterase-activity-dpph-radicals-and-iron-ii-chelation
#4
Srinivas Kantham, Stephen Chan, Gawain McColl, Jared Miles, Suresh Kumar Veliyath, Girdhar Singh Deora, Satish N Dighe, Samira Khabbazi, Marie-Odile Parat, Benjamin P Ross
The biphenyl neolignan honokiol is a neuroprotectant which has been proposed as a treatment for central nervous system disorders such as Alzheimer's disease (AD). The death of cholinergic neurons in AD is attributed to multiple factors, including: accumulation and fibrillation of amyloid beta peptide (Aβ) within the brain; metal ion toxicity; and oxidative stress. In this study, we used a transgenic Caenorhabditis elegans model expressing full length Aβ42 as a convenient in vivo system for examining the effect of honokiol against Aβ-induced toxicity...
June 26, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28650628/synthesis-and-evaluation-of-new-fluorine-18-labeled-verapamil-analogs-to-investigate-the-function-of-p-glycoprotein-in-the-blood-brain-barrier
#5
Renske Maria Raaphorst, Gert Luurtsema, Robert C Schuit, Esther J M Kooijman, Philip H Elsinga, Adriaan A Lammertsma, Albert D Windhorst
P-glycoprotein is an efflux transporter located in the blood-brain barrier. (R)-[(11)C]verapamil is widely used as a PET tracer to investigate its function in patients with epilepsy, Alzheimer's disease and other neurodegenerative diseases. Currently it is not possible to use this successful tracer in clinics without a cyclotron, because of the short half-life of carbon-11. We developed two new fluorine-18 labeled (R)-verapamil analogs, with the benefit of a longer half-life. The synthesis of (R)-N-[(18)F]fluoroethylverapamil ([(18)F]1) and (R)-O-[(18)F]fluoroethylnorverapamil ([(18)F]2), has been described...
June 26, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28650335/development-of-ad-like-symptoms-following-co-administration-of-alcl3-and-d-gal-in-rats-a-neurochemical-biochemical-and-behavioural-study
#6
Laraib Liaquat, Saara Ahmad, Sadia Sadir, Zehra Batool, Saima Khaliq, Saiqa Tabassum, Shaista Emad, Syeda Madiha, Sidrah Shahzad, Saida Haider
Alzheimer's disease (AD) is an age-related neurodegenerative disorder associated with neurochemical and neurobehavioural alterations. Aluminium (Al) is considered as a contributing factor in the etiology of several neurodegenerative disorders like AD. D-galactose (D-gal) is a physiological nutrient but over supply induces some neurochemical and biochemical changes that exacerbate natural aging process. In this study, we aimed to develop AD animal model by co-administration of Al and D-gal in rats. Male albino Wistar rats were intraperitoneally injected with AlCl3 and D-gal at a dose of 150mg/kg and 300mg/kg respectively for one week...
March 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28650319/somatostatin-binds-to-the-human-amyloid-%C3%AE-peptide-and-favors-the-formation-of-distinct-oligomers
#7
Hansen Wang, Lisa D Muiznieks, Punam Ghosh, Declan Williams, Michael Solarski, Andrew Fang, Alejandro Ruiz-Riquelme, Régis Pomès, Joel C Watts, Avi Chakrabartty, Holger Wille, Simon Sharpe, Gerold Schmitt-Ulms
The amyloid β peptide (Aβ) is a key player in the etiology of Alzheimer disease (AD), yet a systematic investigation of its molecular interactions has not been reported. Here we identified by quantitative mass spectrometry proteins in human brain extract that bind to oligomeric Aβ1-42 (oAβ1-42) and/or monomeric Aβ1-42 (mAβ1-42) baits. Remarkably, the cyclic neuroendocrine peptide somatostatin-14 (SST14) was observed to be the most selectively enriched oAβ1-42 binder. The binding interface comprises a central tryptophan within SST14 and the N-terminus of Aβ1-42...
June 26, 2017: ELife
https://www.readbyqxmd.com/read/28650104/alzheimer-s-disease-and-metabolic-syndrome-a-link-from-oxidative-stress-and-inflammation-to-neurodegeneration
#8
REVIEW
Eduardo Rojas-Gutierrez, Guadalupe Muñoz-Arenas, Samuel Treviño, Blanca Espinosa, Raúl Chavez, Karla Rojas, Gonzalo Flores, Alfonso Díaz, Jorge Guevara
Alzheimer's disease (AD) is the most common cause of dementia and one of the most important causes of morbidity and mortality among the aging population. AD diagnosis is made post-mortem, and the two pathologic hallmarks, particularly evident in the end stages of the illness, are amyloid plaques and neurofibrillary tangles (NFT). Currently, there is no curative treatment for AD. Additionally, there is a strong relation between oxidative stress, metabolic syndrome (MetS) and AD. The high levels of circulating lipids and glucose imbalances amplify lipid peroxidation that gradually diminishes the antioxidant systems, causing high levels of oxidative metabolism that affects cell structure, leading to neuronal damage...
June 26, 2017: Synapse
https://www.readbyqxmd.com/read/28649604/combined-immunotherapy-with-anti-insulin-resistance-therapy-as-a-novel-therapeutic-strategy-against-neurodegenerative-diseases
#9
Yoshiki Takamatsu, Gilbert Ho, Wakako Koike, Shuei Sugama, Takato Takenouchi, Masaaki Waragai, Jianshe Wei, Kazunari Sekiyama, Makoto Hashimoto
Protein aggregation is a pathological hallmark of and may play a central role in the neurotoxicity in age-associated neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Accordingly, inhibiting aggregation of amyloidogenic proteins, including amyloid β and α-synuclein, has been a main therapeutic target for these disorders. Among various strategies, amyloid β immunotherapy has been extensively investigated in Alzheimer's disease, followed by similar studies of α-synuclein in Parkinson's disease...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/28649597/early-diagnosis-of-mild-cognitive-impairment-and-alzheimer-s-disease-based-on-salivary-lactoferrin
#10
Eva Carro, Fernando Bartolomé, Félix Bermejo-Pareja, Alberto Villarejo-Galende, José Antonio Molina, Pablo Ortiz, Miguel Calero, Alberto Rabano, José Luis Cantero, Gorka Orive
INTRODUCTION: The Alzheimer's disease (AD) process is likely initiated many years before clinical onset. Biomarkers of preclinical disease are critical for the development of disease-modifying or even preventative therapies. Current biomarkers for early disease, including cerebrospinal fluid tau and amyloid β (Aβ) levels, structural and functional magnetic resonance imaging, and the use of brain amyloid imaging, are limited because they are very invasive or expensive. Noninvasive biomarkers may be a more accessible alternative, but none can currently detect preclinical AD with the required sensitivity and specificity...
2017: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/28649128/lx2343-alleviates-cognitive-impairments-in-ad-model-rats-by-inhibiting-oxidative-stress-induced-neuronal-apoptosis-and-tauopathy
#11
Xiao-Dan Guo, Guang-Long Sun, Ting-Ting Zhou, Yi-Yang Wang, Xin Xu, Xiao-Fan Shi, Zhi-Yuan Zhu, Vatcharin Rukachaisirikul, Li-Hong Hu, Xu Shen
Alzheimer's disease (AD) is a progressive neurodegenerative disease leading to the irreversible loss of brain neurons and cognitive abilities, and the vicious interplay between oxidative stress (OS) and tauopathy is believed to be one of the major players in AD development. Here, we demonstrated the capability of the small molecule N-(1,3-benzodioxol-5-yl)-2-[5-chloro-2-methoxy(phenylsulfonyl)anilino]acetamide (LX2343) to ameliorate the cognitive dysfunction of AD model rats by inhibiting OS-induced neuronal apoptosis and tauopathy...
June 26, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28649025/a%C3%AE-plaque-selective-nir-fluorescence-probe-to-differentiate-alzheimer-s-disease-from-tauopathies
#12
K Rajasekhar, Nagarjun Narayanaswamy, N Arul Murugan, Keith Viccaro, Hyoung-Gon Lee, Kavita Shah, Thimmaiah Govindaraju
Selective detection and staining of toxic amyloid plaques, a potential biomarker present in the Alzheimer's disease (AD) brain is crucial for both clinical diagnosis and monitoring AD disease progression. Herein, we report a coumarin-quinoline (CQ) conjugate-based turn-on near-infrared (NIR) fluorescence probe for specific detection of β-amyloid (Aβ) aggregates. CQ probe is highly sensitive and exhibits ~100-fold fluorescence enhancement in vitro upon binding Aβ aggregates with enhanced quantum yield. Furthermore, the probe has ~10-fold higher binding affinity towards Aβ aggregates (86nM) compared to commonly used Thioflavin T...
June 17, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28648936/diagnostic-pathology-of-alzheimer-s-disease-from-routine-microscopy-to-immunohistochemistry-and-experimental-correlations
#13
Gerard Nuovo, Bernard Paniccia, Louisa Mezache, Maria Quiñónez, James Williams, Paige Vandiver, Paolo Fadda, Vicky Amann
The absence of any histologic correlate for Alzheimer's disease despite its commonness and severe clinical sequelae may offers clues to its etiology. Recent evidence strongly suggests that the central event of this disease is the hyperphosphorylation of neuronal tau protein and not the beta amyloid precipitates. In each case, essential and soluble neuronal proteins derivatives form insoluble aggregates that can readily be detected by immunohistochemistry using antibodies specific for the misfolded proteins...
June 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28648388/heterozygous-knockout-of-cytosolic-phospholipase-a2%C3%AE-attenuates-alzheimer-s-disease-pathology-in-app-ps1-transgenic-mice
#14
Baoxi Qu, Yunhua Gong, Jassica M Gill, Kimbra Kenney, Ramon Diaz-Arrastia
Cytosolic Phospholipase A2α (cPLA2α) is a key enzyme in regulation of inflammation process and neuromembrane homeostasis, both of which are critical in pathogenesis of Alzheimer's diseases. By hybride APP/PS1 Tg-AD mice with cPLA2α knockout mice, three lines of APP/PS1 Tg-AD mice were produced with genotypes of cPLA2α +/+, cPLA2α +/- and cPLA2α-/-. Compared to cPLA2α +/+ Tg-AD mice, the amyloid plaque formation was significantly downregulated in the brain of cPLA2α+/- Tg-AD mice, but not in cPLA2α -/- Tg-AD mice...
June 22, 2017: Brain Research
https://www.readbyqxmd.com/read/28647892/postprandial-hypotension-in-neurological-disorders-systematic-review-and-meta-analysis
#15
REVIEW
Antun Pavelić, Magdalena Krbot Skorić, Luka Crnošija, Mario Habek
PURPOSE: Postprandial hypotension (PPH) has been associated with increased risk of syncope, falls, stroke, angina and mortality. As the majority of patients with PPH are asymptomatic, the diagnosis is often overlooked. The aim of this study was to perform a systematic review and meta-analysis of available scientific evidence on the likelihood of PPH in neurological diseases. METHODS: A systematic review of the literature (PubMed library, Cochrane Database for Systematic Reviews and Cochrane Central Register of Controlled Trials for results up to January 2017) identified 327 studies, of which 11 reported the frequency of PPH in patients with neurological diseases compared to healthy controls...
June 24, 2017: Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society
https://www.readbyqxmd.com/read/28647556/synapsin-i-phosphorylation-is-dysregulated-by-beta-amyloid-oligomers-and-restored-by-valproic-acid
#16
Jade Marsh, Saifuddien Haji Bagol, Robin S B Williams, George Dickson, Pavlos Alifragis
Alzheimer's disease is the most prevalent form of dementia in the elderly but the precise causal mechanisms are still not fully understood. Growing evidence supports a significant role for Aβ42 oligomers in the development and progression of Alzheimer's. For example, intracellular soluble Aβ oligomers are thought to contribute to the early synaptic dysfunction associated with Alzheimer's disease, but the molecular mechanisms underlying this effect are still unclear. Here, we identify a novel mechanism that contributes to our understanding of the reported synaptic dysfunction...
June 21, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28647555/normalizing-the-gene-dosage-of-dyrk1a-in-a-mouse-model-of-down-syndrome-rescues-several-alzheimer-s-disease-phenotypes
#17
Susana García-Cerro, Noemí Rueda, Verónica Vidal, Sara Lantigua, Carmen Martínez-Cué
The intellectual disability that characterizes Down syndrome (DS) is primarily caused by prenatal changes in central nervous system growth and differentiation. However, in later life stages, the cognitive abilities of DS individuals progressively decline due to accelerated aging and the development of Alzheimer's disease (AD) neuropathology. The AD neuropathology in DS has been related to the overexpression of several genes encoded by Hsa21 including DYRK1A (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A), which encodes a protein kinase that performs crucial functions in the regulation of multiple signaling pathways that contribute to normal brain development and adult brain physiology...
June 21, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28647411/hippocampal-5-ht1a-receptor-expression-changes-in-prodromal-stages-of-alzheimer-s-disease-beneficial-or-deleterious
#18
REVIEW
M Verdurand, L Zimmer
There is increasing evidence that the serotonergic system is highly dysfunctional in Alzheimer's disease (AD), and this could be related to cognitive impairments associated with dementia. Of the various serotonin receptors, 5-HT1A receptors are relevant to AD as they are highly expressed in the human hippocampus and are known to be involved in the regulation of memory processes. This review will discuss the involvement of 5-HT1A receptors in AD at several levels (post-mortem, in-vivo imaging, animal models)...
June 21, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28647363/cadps2-gene-expression-is-oppositely-regulated-by-lrrk2-and-alpha-synuclein
#19
Julia Obergasteiger, Christa Überbacher, Peter P Pramstaller, Andrew A Hicks, Corrado Corti, Mattia Volta
The Ca(2+)-dependent activator protein for secretion 2 (CADPS2) is a member of the CAPS/CADPS protein family that play crucial roles in synaptic vesicle dynamics. Genomic variability in the CADPS2 gene has been associated to autism spectrum disorders and Alzheimer's disease, both characterized by altered neurotransmission. Biological evidence also linked CADPS2 to Parkinson's disease (PD), as a disease-causing mutation in leucine-rich repeat kinase 2 (LRRK2) was reported to increase CADPS2 gene and protein expression...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28647031/cover-story-towards-a-preventive-treatment-of-alzheimer-s-disease-with-multi-functional-liposomes
#20
EDITORIAL
Kinam Park
No abstract text is available yet for this article.
July 28, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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