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https://www.readbyqxmd.com/read/28550295/effects-of-protein-corona-on-iapp-amyloid-aggregation-fibril-remodelling-and-cytotoxicity
#1
Emily H Pilkington, Yanting Xing, Bo Wang, Aleksandr Kakinen, Miaoyi Wang, Thomas P Davis, Feng Ding, Pu Chun Ke
Aggregation of islet amyloid polypeptide (IAPP), a peptide hormone co-synthesized and co-stored with insulin in pancreatic cells and also co-secreted to the circulation, is associated with beta-cell death in type-2 diabetes (T2D). In T2D patients IAPP is found aggregating in the extracellular space of the islets of Langerhans. Although the physiological environments of these intra- and extra-cellular compartments and vascular systems significantly differ, the presence of proteins is ubiquitous but the effects of protein binding on IAPP aggregation are largely unknown...
May 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28546539/microbiota-modulation-counteracts-alzheimer-s-disease-progression-influencing-neuronal-proteolysis-and-gut-hormones-plasma-levels
#2
Laura Bonfili, Valentina Cecarini, Sara Berardi, Silvia Scarpona, Jan S Suchodolski, Cinzia Nasuti, Dennis Fiorini, Maria Chiara Boarelli, Giacomo Rossi, Anna Maria Eleuteri
Gut microbiota has a proven role in regulating multiple neuro-chemical pathways through the highly interconnected gut-brain axis. Oral bacteriotherapy thus has potential in the treatment of central nervous system-related pathologies, such as Alzheimer's disease (AD). Current AD treatments aim to prevent onset, delay progression and ameliorate symptoms. In this work, 3xTg-AD mice in the early stage of AD were treated with SLAB51 probiotic formulation, thereby affecting the composition of gut microbiota and its metabolites...
May 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28538095/high-resolution-structures-of-the-amyloid-%C3%AE-1-42-dimers-from-the-comparison-of-four-atomistic-force-fields
#3
Viet Hoang Man, Phuong Hoang Nguyen, Philippe Derreumaux
The dimer of the amyloid-beta peptide Aβ of 42 residues is the smallest toxic species in Alzheimer's disease, but its equilibrium structures are unknown. Here we determined the equilibrium ensembles generated by the four atomistic OPLS-AA, CHARMM22*, AMBER99sb-ildn and AMBERsb14 force fields with the TIP3P water model. Based on 144 microsecond replica exchange molecular dynamics simulations (with 750 ns per replica), we find that the four force fields lead to random coil ensembles with calculated cross-collision sections, hydrodynamics properties and small-angle X-ray scattering profiles independent on the force field...
May 24, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28536682/a-case-of-intramural-coronary-amyloidosis-associated-with-hemodialysis
#4
Faisal M Huq Ronny, George Kleinman, Paul James Kurtin, John Thomas Fallon
Dialysis-related amyloidosis predominantly occurs in osteo-articular structures and dialysis-related amyloid (DRA) substances also deposit in extra-articular tissues. Clinical manifestations of DRA include odynophagia, gastrointestinal hemorrhage, intestinal obstruction, kidney stones, myocardial dysfunction, and subcutaneous tumors. The pathological characteristics of DRA in the heart of hemodialysis patients have rarely been reported. We report the case of a 73-year-old female with a history of cerebral palsy and end-stage renal disease status post two failed renal transplants who had been on hemodialysis for 30 years...
January 2017: Autopsy & case reports
https://www.readbyqxmd.com/read/28535786/biochemical-markers-in-vascular-cognitive-impairment-associated-with-subcortical-small-vessel-disease-a-consensus-report
#5
A Wallin, E Kapaki, M Boban, S Engelborghs, D M Hermann, B Huisa, M Jonsson, M G Kramberger, L Lossi, B Malojcic, S Mehrabian, A Merighi, E B Mukaetova-Ladinska, G P Paraskevas, B O Popescu, R Ravid, L Traykov, G Tsivgoulis, G Weinstein, A Korczyn, M Bjerke, G Rosenberg
BACKGROUND: Vascular cognitive impairment (VCI) is a heterogeneous entity with multiple aetiologies, all linked to underlying vascular disease. Among these, VCI related to subcortical small vessel disease (SSVD) is emerging as a major homogeneous subtype. Its progressive course raises the need for biomarker identification and/or development for adequate therapeutic interventions to be tested. In order to shed light in the current status on biochemical markers for VCI-SSVD, experts in field reviewed the recent evidence and literature data...
May 23, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28534925/osmotin-loaded-magnetic-nanoparticles-with-electromagnetic-guidance-for-the-treatment-of-alzheimer-s-disease
#6
Faiz Ul Amin, Ali Kafash Hoshiar, Ton Duc Do, Yeongil Noh, Shahid Ali Shah, Muhammad Sohail Khan, Jungwon Yoon, Myeong Ok Kim
Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregated amyloid beta (Aβ) in the brain. Here, we describe for the first time the development of a new, pioneering nanotechnology-based drug delivery approach for potential therapies for neurodegenerative diseases, particularly AD. We demonstrated the delivery of fluorescent carboxyl magnetic Nile Red particles (FMNPs) to the brains of normal mice using a functionalized magnetic field (FMF) composed of positive- and negative-pulsed magnetic fields generated by electromagnetic coils...
May 23, 2017: Nanoscale
https://www.readbyqxmd.com/read/28534431/ameliorating-effect-of-anti-alzheimer-s-drugs-on-the-bidirectional-association-between-type-2-diabetes-mellitus-and-alzheimer-s-disease
#7
Amira S Ahmed, Rehab M Elgharabawy, Amal H Al-Najjar
Mild to severe forms of nervous system damage were exhibited by approximately 60-70% of diabetics. It is important to understand the association between type 2 diabetes mellitus and Alzheimer's disease. The aim of the present work is to understand the bidirectional association between type 2 diabetes and Alzheimer's disease pathogenesis, that was monitored by glycaemic status, lipid profile, amyloid beta 40 and 42 (Aβ40 and Aβ42), C-reactive protein, total creatine kinase, total lactate dehydrogenase, D-dimer and magnesium measurements, to assess the association between theses biochemical markers and each other, to estimate the possibility of utilizing the amyloid beta as biochemical marker of T2D in Alzheimer's patients, and to evaluate the effect of piracetam and memantine drugs on diabetes mellitus...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28530185/effect-of-gnp-functionalisation-and-multiple-n-methylation-of-%C3%AE-amyloid-residue-32-37-on-gram-positive-bacterium
#8
Nanjundaswamy Marishetty Hemmaragala, Heidi Abrahamse, Blassan P George
In the previous report, the authors showed the gold nanoparticle (GNP) functionalised multiple N-methylated fragments of the residue (32-37) of beta (β)-amyloid protein (1-42), CGGIGLMVG and CGGGGGIGLMVG toward disruption of β-amyloid (1-42), the predominant component of senile plaques. Herein the in vitro antimicrobial activities of both normal and multiple N-methylated sequences of CGGIGLMVG and CGGGGGIGLMVG were screened and it was found that all the eight sequences including four (non-functionalised with GNP) to possess activity against both Gram-positive [Staphylococcus aureus (ATCC 43300) and Enterococcus faecalis (ATCC 5129)] and Gram-negative [Escherichia coli (ATCC 35218), Pseudomonas aeruginosa (ATCC 27853) and Klebsiella pneumoniae (ATCC 700603)] bacteria...
June 2017: IET Nanobiotechnology
https://www.readbyqxmd.com/read/28528948/multi-functional-activities-of-citrus-flavonoid-narirutin-in-alzheimer-s-disease-therapeutics-an-integrated-screening-approach-and-in-vitro-validation
#9
Sandipan Chakraborty, Soumalee Basu
Alzheimer's disease (AD) is a complex disorder and the disease mechanism is yet to be properly characterized. Over the years, "amyloid cascade" emerges as principal pathogenic event in AD. β-Secretase 1 (BACE1) controls the rate-limiting step in amyloid beta (Aβ) generation and Aβ rapidly aggregates to form neurotoxic amyloid fibrils. Oxidative stress is one of the principal mediators of the observed neurotoxicity of amyloid fibril. The disease pathogenesis involves induction of multiple signaling cascades and the cross-talk therein...
May 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28528185/simvastatin-ameliorate-memory-deficits-and-inflammation-in-clinical-and-mouse-model-of-alzheimer-s-disease-via-modulating-the-expression-of-mir-106b
#10
Wenzhong Huang, Zhenyu Li, Liandong Zhao, Wei Zhao
BACKGROUND: Alzheimer's disease (AD) as a neurodegenerative brain disorder is a devastating pathology leading to disastrous cognitive impairments and dementia, and several studies have shown that AD is closely related to the inflammation, so anti-inflammatory treatment may provide therapeutic benefits. In this study, the effect of simvastatin on inflammation was investigated and the underlying mechanisms were explored. METHODS: First, we tested the effect of simvastatin on AD in clinical research...
May 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28527630/diagnostic-accuracy-of-csf-neurofilament-light-chain-protein-in-the-biomarker-guided-classification-system-for-alzheimer-s-disease
#11
Simone Lista, Nicola Toschi, Filippo Baldacci, Henrik Zetterberg, Kaj Blennow, Ingo Kilimann, Stefan J Teipel, Enrica Cavedo, Antonio Melo Dos Santos, Stéphane Epelbaum, Foudil Lamari, Bruno Dubois, Roberto Floris, Francesco Garaci, Harald Hampel
We assessed the diagnostic accuracy of cerebrospinal fluid (CSF) neurofilament light chain (NFL) protein in the classification of patients with Alzheimer's disease (AD) and cognitively healthy control individuals (HCs) and patients with frontotemporal dementia (FTD) as comparisons. Particularly, we tested the performance of CSF NFL concentration in differentiating patient groups stratified by fluid biomarker profiles, independently of the severity of cognitive impairment (mild cognitive impairment (MCI) and AD dementia individuals), using a biomarker-guided descriptive classification system for AD...
May 17, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28526839/fluorescence-correlation-spectroscopy-reveals-a-cooperative-unfolding-of-monomeric-amyloid-%C3%AE-42-with-a-low-gibbs-free-energy
#12
Mario Schneider, Stefan Walta, Chris Cadek, Walter Richtering, Dieter Willbold
The amyloid-beta peptide (Aβ) plays a major role in the progression of Alzheimer's disease. Due to its high toxicity, the 42 amino acid long isoform Aβ42 has become of considerable interest. The Aβ42 monomer is prone to aggregation down to the nanomolar range which makes conventional structural methods such as NMR or X-ray crystallography infeasible. Conformational information, however, will be helpful to understand the different aggregation pathways reported in the literature and will allow to identify potential conditions that favour aggregation-incompetent conformations...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28523718/does-sleep-disturbance-affect-the-amyloid-clearance-mechanisms-in-alzheimer-s-disease
#13
REVIEW
Burak Yulug, Lutfu Hanoglu, Ertugrul Kilic
Sleep is one of the important factors that play a key role in AD pathogenesis. However, it is still unclear whether poor quality sleep may overlap with sleep disturbances in the underlying dysfunctional mechanisms of amyloid beta (Aβ) clearance metabolism. Here, we aimed to evaluate the current evidence on the role of sleep deprivation in amyloid beta (Aβ) clearance metabolism. To that end, we discussed possible mechanisms underlying the bidirectional interaction between the sleep deprivation and amyloid beta (Aβ) clearance pathways...
May 18, 2017: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/28523253/cell-therapy-products-in-alzheimer-disease
#14
REVIEW
Hyeon Jin Song, Tae-Hee Kim, Hae-Hyeog Lee, Jun-Mo Kim, Yoo Jin Park, Arum Lee, Soo Ah Kim, Hye Ji Choi
We are rapidly becoming an aging society, with the ongoing increase in challenges of the elderly. The age-related cognitive decline in accordance with aging society is of major importance in public health. Recent studies have proved the impacts of sex-steroid hormone on the brain; compliant with aging, menopause and decrease in estrogen have an effect on the occurrence and prevention of Alzheimer's disease. A new hypothesis states that Alzheimer's disease is a postmenopausal dementia, and is a negative form of estrogen deficiency...
April 2017: Journal of Menopausal Medicine
https://www.readbyqxmd.com/read/28520803/multiple-modality-biomarker-prediction-of-cognitive-impairment-in-prospectively-followed-de-novo-parkinson-disease
#15
Chelsea Caspell-Garcia, Tanya Simuni, Duygu Tosun-Turgut, I-Wei Wu, Yu Zhang, Mike Nalls, Andrew Singleton, Leslie A Shaw, Ju-Hee Kang, John Q Trojanowski, Andrew Siderowf, Christopher Coffey, Shirley Lasch, Dag Aarsland, David Burn, Lana M Chahine, Alberto J Espay, Eric D Foster, Keith A Hawkins, Irene Litvan, Irene Richard, Daniel Weintraub
OBJECTIVES: To assess the neurobiological substrate of initial cognitive decline in Parkinson's disease (PD) to inform patient management, clinical trial design, and development of treatments. METHODS: We longitudinally assessed, up to 3 years, 423 newly diagnosed patients with idiopathic PD, untreated at baseline, from 33 international movement disorder centers. Study outcomes were four determinations of cognitive impairment or decline, and biomarker predictors were baseline dopamine transporter (DAT) single photon emission computed tomography (SPECT) scan, structural magnetic resonance imaging (MRI; volume and thickness), diffusion tensor imaging (mean diffusivity and fractional anisotropy), cerebrospinal fluid (CSF; amyloid beta [Aβ], tau and alpha synuclein), and 11 single nucleotide polymorphisms (SNPs) previously associated with PD cognition...
2017: PloS One
https://www.readbyqxmd.com/read/28515688/insulin-resistance-as-a-link-between-amyloid-beta-and-tau-pathologies-in-alzheimer-s-disease
#16
Roger J Mullins, Thomas C Diehl, Chee W Chia, Dimitrios Kapogiannis
Current hypotheses and theories regarding the pathogenesis of Alzheimer's disease (AD) heavily implicate brain insulin resistance (IR) as a key factor. Despite the many well-validated metrics for systemic IR, the absence of biomarkers for brain-specific IR represents a translational gap that has hindered its study in living humans. In our lab, we have been working to develop biomarkers that reflect the common mechanisms of brain IR and AD that may be used to follow their engagement by experimental treatments...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28514851/blood-brain-barrier-penetrating-biologic-tnf-%C3%AE-inhibitor-for-alzheimer-s-disease
#17
Rudy Chang, Jillian Knox, Jae Chang, Aram Derbedrossian, Vitaly Vasilevko, David Cribbs, Ruben J Boado, William M Pardridge, Rachita Sumbria
OBJECTIVE: Tumor necrosis factor alpha (TNF-α) driven processes are involved at multiple stages of Alzheimer's disease (AD) pathophysiology and disease progression. Biologic TNF-α inhibitors (TNFIs) are the most potent class of TNFIs but cannot be developed for AD since these macromolecules do not cross the blood-brain barrier (BBB). A BBB-penetrating TNFI was engineered by the fusion of the extracellular domain of the type II human TNF receptor (TNFR) to a chimeric monoclonal antibody (MAb) against the mouse transferrin receptor (TfR), designated as the cTfRMAb-TNFR fusion protein...
May 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28514831/hypericum-perforatum-extract-attenuates-behavioral-biochemical-and-neurochemical-abnormalities-in-aluminum-chloride-induced-alzheimer-s-disease-rats
#18
Zheng Cao, Fan Wang, Chunyu Xiu, Jian Zhang, Yanfei Li
Alzheimer's disease (AD) is a progressive and ultimately fatal neurodegenerative diseases. Aluminum, a neurotoxic metal, is considered as the pathological hallmark and contributing factor of AD. Hypericum perforatum extract (HPE) is a neuroprotective agent that can prevent neurodegenerative pathologies through antioxidants, anti-inflammatory and regulating neurotransmitter release in animal model of neuropathy. The present study aimed to identify the potential neuroprotective of HPE on AlCl3-induced AD rats...
May 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28511918/molecular-imaging-of-serotonin-degeneration-in-mild-cognitive-impairment
#19
Gwenn S Smith, Frederick S Barrett, Jin Hui Joo, Najlla Nassery, Alena Savonenko, Devin J Sodums, Christopher M Marano, Cynthia A Munro, Jason Brandt, Michael A Kraut, Yun Zhou, Dean F Wong, Clifford I Workman
Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions, as well as the cell bodies of origin (raphe nuclei)...
May 13, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28511119/effects-of-breviscapine-on-amyloid-beta-1-42-induced-alzheimer-s-disease-mice-a-hplc-qtof-ms-based-plasma-metabonomics-study
#20
Hongjun Xia, Lingling Wu, Mengying Chu, Huimin Feng, Chunliang Lu, Qinghe Wang, Minghai He, Xiaoqun Ge
Herba Erigerontis has long been used to cure apoplexy hemiplegia and precordial pain in China. In addition, the bioactivities of its total flavonoids-breviscapine included inhibiting amyloid beta (Aβ) fibril formation, antioxidation and metal chelating, which are beneficial to treat Alzheimer's disease (AD). Hence, A HPLC-QTOF-MS based plasma metabonomics approach was applied to investigate the neuroprotective effects of breviscapine on intracerebroventricular injection of aggregated Aβ 1-42 induced AD mice for the first time in the study...
July 1, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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