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https://www.readbyqxmd.com/read/29334419/a-metallo-pro-drug-to-target-cu-ii-in-the-context-of-alzheimer-s-disease
#1
Amandine Conte-Daban, Vinita Ambike, Régis Guillot, Nicolas Delsuc, Clotilde Policar, Christelle Hureau
Alzheimer's disease and oxidative stress are connected. In the present communication, we report the use of a Mn(II)-based superoxide dismutase mimic ([MnII(L)]+, 1+) as a pro-drug candidate to target Cu(II) associated events, i.e. Cu(II)-induced formation of reactive oxygen species (ROS) and modulation of the amyloid-beta (Abeta) peptide aggregation. Complex 1+ is able to remove Cu(II) from Abeta, stop ROS and prevent alteration of Abeta aggregation as would do the corresponding free ligand LH. Using 1+ instead of LH in further biological applications would have the double advantage to avoid the cell toxicity of LH and to benefit from its proved SOD-like activity...
January 15, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29334222/on-line-preconcentration-in-capillaries-by-multiple-large-volume-sample-stacking-an-alternative-to-immunoassays-for-quantification-of-amyloid-beta-peptides-biomarkers-in-cerebrospinal-fluid
#2
Cedric Crosnier de Lassichere, Thanh Duc Mai, Markus Otto, Myriam Taverna
A novel electrokinetic preconcentration approach, so-called multiple pressure-assisted large-volume sample stacking with an electroosmotic flow pump (M-PA-LVSEP), was developed to allow in-capillary enrichment and separation of analytes from unlimited sample volumes. With this approach, the inherent limitation of in-capillary electrokinetic preconcentrations to the separation capillary volume can be overcome. The M-PA-LVSEP protocol relies on repeated cycles of pressure-assisted electroosmotic pumping and injection of extremely large sample volumes for analyte stacking and sample matrix removal...
January 15, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29332584/multicomponent-reactions-for-multitargeted-compounds-for-alzheimer-s-disease
#3
Lhassane Ismaili, Maria do Carmo Carreiras
Alzheimer's disease (AD) is a multifactorial and fatal neurodegenerative disorder affecting around 35 million people worldwide, which is characterized by decline of cholinergic function, deregulation of amyloid beta (Aβ) oligomers formation and Aβ fibril deposition. Multi-target--directed ligands (MTDLs) have emerged as an original strategy for developing new therapeutic agents on AD. Multicomponent reactions (MCRs) are a useful alternative to sequential multistep syntheses, allowing scaffold diversity and a rapid and easy access to biologically relevant compounds...
January 12, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29332579/alzheimer-s-disease-a-systemic-review-of-substantial-therapeutic-targets-and-the-leading-multi-functional-molecules
#4
Tarana Umar, Nasimul Hoda
Alzheimer's disease (AD) is a fatal neurodegenerative disorder, having a complex aetiology with numerous possible drug targets. There are targets that have been known for years while more new targets and theories have also emerged. Beta amyloid and cholinesterases are the most significant biological targets for finding curative treatment of AD. The major class of drugs used for AD till now has been the Cholinesterase (ChE) inhibitors. Other prevailing models of molecular pathogenesis in AD include neurofibrillary tangles (NFTs) and amyloid deposition, tryptophan degradation pathway, kinase and phosphatase activity imbalance and neuroinflammation...
January 12, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29330135/apbb2-is-associated-with-amphetamine-use-and-plasma-beta-amyloids-in-patients-receiving-methadone-maintenance-treatment
#5
Chia-Chen Liu, Chiu-Ping Fang, Tung-Hsia Liu, Hsiang-Wei Kuo, Shu Chi Liu, Sheng-Chang Wang, Andrew C H Chen, Yu-Li Liu
APBB2, amyloid beta (A4) precursor protein-binding family B member 2, has been reported to be associated with opioid dependence. In this study, we reported the first time that the genetic variants in the APBB2 gene were associated with use of amphetamine in opioid dependent patients undergoing methadone maintenance treatment (MMT). 344 heroin-dependent patients undergoing MMT were recruited and assessed for use of amphetamine and opioids by urine toxicology, withdrawal severity, and side effects. DNAs were genome-widely genotyped for all patients...
January 9, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29329580/evidence-for-the-activation-of-pyroptotic-and-apoptotic-pathways-in-rpe-cells-associated-with-nlrp3-inflammasome-in-the-rodent-eye
#6
Jiangyuan Gao, Jing Z Cui, Eleanor To, Sijia Cao, Joanne A Matsubara
BACKGROUND: Age-related macular degeneration (AMD) is a devastating eye disease causing irreversible vision loss in the elderly. Retinal pigment epithelium (RPE), the primary cell type that is afflicted in AMD, undergoes programmed cell death in the late stages of the disease. However, the exact mechanisms for RPE degeneration in AMD are still unresolved. The prevailing theories consider that each cell death pathway works independently and without regulation of each other. Building upon our previous work in which we induced a short burst of inflammasome activity in vivo, we now investigate the effects of prolonged inflammasome activity on RPE cell death mechanisms in rats...
January 12, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29328990/the-amyloidogenicity-of-the-influenza-virus-pb1-derived-peptide-sheds-light-on-its-antiviral-activity
#7
Yana A Zabrodskaya, Dmitry V Lebedev, Marja A Egorova, Aram A Shaldzhyan, Alexey V Shvetsov, Alexander I Kuklin, Daria S Vinogradova, Nikolay V Klopov, Oleg V Matusevich, Taisiia A Cheremnykh, Rajeev Dattani, Vladimir V Egorov
The influenza virus polymerase complex is a promising target for new antiviral drug development. It is known that, within the influenza virus polymerase complex, the PB1 subunit region from the 1st to the 25th amino acid residues has to be is in an alpha-helical conformation for proper interaction with the PA subunit. We have previously shown that PB1(6-13) peptide at low concentrations is able to interact with the PB1 subunit N-terminal region in a peptide model which shows aggregate formation and antiviral activity in cell cultures...
January 8, 2018: Biophysical Chemistry
https://www.readbyqxmd.com/read/29325805/reduced-plaque-size-and-inflammation-in-the-app23-mouse-model-for-alzheimer-s-disease-after-chronic-application-of-polymeric-nanoparticles-for-cns-targeted-zinc-delivery
#8
Antonietta Vilella, Daniela Belletti, Ann Katrin Sauer, Simone Hagmeyer, Tasnuva Sarowar, Martina Masoni, Natalia Stasiak, John J E Mulvihill, Barbara Ruozi, Flavio Forni, Maria Angela Vandelli, Giovanni Tosi, Michele Zoli, Andreas M Grabrucker
A local dyshomeostasis of zinc ions in the vicinity of amyloid aggregates has been proposed in Alzheimer's disease (AD) due to the sequestration of zinc in senile plaques. While an increase in zinc levels may promote the aggregation of amyloid beta (Aβ), increased brain zinc might also be beneficial rescuing some pathological alterations caused by local zinc deficiency. For example, increased Aβ degradation by metalloproteinases, and a reduction in inflammation can be hypothesized. In addition, zinc may allow a stabilization of the number of synapses in AD brains...
December 27, 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29325447/longitudinal-association-of-amyloid-beta-and-anxious-depressive-symptoms-in-cognitively-normal-older-adults
#9
Nancy J Donovan, Joseph J Locascio, Gad A Marshall, Jennifer Gatchel, Bernard J Hanseeuw, Dorene M Rentz, Keith A Johnson, Reisa A Sperling
OBJECTIVE: To understand the role of depressive symptoms in preclinical Alzheimer's disease, it is essential to define their temporal relationship to Alzheimer's proteinopathies in cognitively normal older adults. The study objective was to examine associations of brain amyloid beta and longitudinal measures of depression and depressive symptom clusters in a cognitively normal sample of older adults. METHOD: A total of 270 community-dwelling, cognitively normal elderly individuals underwent baseline Pittsburgh compound B (PiB) positron emission tomography (PET) measures of cortical aggregate amyloid beta and annual assessments with the 30-item Geriatric Depression Scale (GDS)...
January 12, 2018: American Journal of Psychiatry
https://www.readbyqxmd.com/read/29324921/the-correlation-of-evans-index-with-csf-protein-levels-and-ventriculomegaly
#10
D Papaoikonomou, E Karypidou, P Megagiannis, F Tsolaki-Tagaraki, S Nenopoulou, O Gkatzima, Magda Tsolaki
OBJECTIVE: The role of ventriculomegaly and its interplay between various dementia entities and their pathogenesis, as well as its correlation to the levels of CSF protein markers, remains to be elucidated. Evans index (EI) is a well-established radiological marker in the diagnosis of idiopathic Normal Pressure Hydrocephalus (iNPH), assessing ventricular enlargement. However, there are no previous studies investigating the correlation between EI, age, beta amyloid (Aβ), tau and phosphorylated-tau (p-tau) proteins in the CSF...
September 2017: Hellenic Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/29324783/sirt3-activator-honokiol-attenuates-%C3%AE-amyloid-by-modulating-amyloidogenic-pathway
#11
Sindhu Ramesh, Manoj Govindarajulu, Tyler Lynd, Gwyneth Briggs, Danielle Adamek, Ellery Jones, Jake Heiner, Mohammed Majrashi, Timothy Moore, Rajesh Amin, Vishnu Suppiramaniam, Muralikrishnan Dhanasekaran
Honokiol (poly-phenolic lignan from Magnolia grandiflora) is a Sirtuin-3 (SIRT3) activator which exhibit antioxidant activity and augment mitochondrial functions in several experimental models. Modern evidence suggests the critical role of SIRT3 in the progression of several metabolic and neurodegenerative diseases. Amyloid beta (Aβ), the precursor to extracellular senile plaques, accumulates in the brains of patients with Alzheimer's disease (AD) and is related to the development of cognitive impairment and neuronal cell death...
2018: PloS One
https://www.readbyqxmd.com/read/29323711/hiv-1-increases-extracellular-amyloid-beta-levels-through-neprilysin-regulation-in-primary-cultures-of-human-astrocytes
#12
Marta Martínez-Bonet, M Ángeles Muñoz-Fernández, Susana Álvarez
Since the success of combined antiretroviral therapy, HIV-1-infected individuals are now living much longer. This increased life expectancy is accompanied by a higher prevalence of HIV-1 associated neurocognitive disorders. Rising too is the incidence in these patients of pathological hallmarks of Alzheimer's disease such as increased deposition of amyloid beta protein (Aβ). Although neurons are major sources of Aβ in the brain, astrocytes are the most numerous glial cells, therefore, even a small level of astrocytic Aβ metabolism could make a significant contribution to brain pathology...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29321508/thrombospondin-1-secreted-by-human-umbilical-cord-blood-derived-mesenchymal-stem-cells-rescues-neurons-from-synaptic-dysfunction-in-alzheimer-s-disease-model
#13
Dong Hyun Kim, Hoon Lim, Dahm Lee, Soo Jin Choi, Wonil Oh, Yoon Sun Yang, Jeong Su Oh, Hyun Ho Hwang, Hong Bae Jeon
Alzheimer's disease (AD) is an incurable neurodegenerative disease characterised clinically by learning and memory impairments. Amyloid beta (Aβ) peptide-induced synaptic dysfunction is a pathological process associated with early-stage AD. Here, we show that paracrine action of human umbilical cord blood-derived-mesenchymal stem cells (hUCB-MSCs) protects the hippocampus from synaptic-density loss in in vitro and in vivo AD models. To identify paracrine factors underlying this rescue effect, we analysed hUCB-MSCs' secretome co-cultured with Aβ42-treated mouse hippocampal neurons...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321137/novel-function-of-ceramide-for-regulation-of-mitochondrial-atp-release-in-astrocytes
#14
Ji-Na Kong, Zhihui Zhu, Yutaka Itokazu, Guanghu Wang, Michael B Dinkins, Liansheng Zhong, Hsuan-Pei Lin, Ahmed Elsherbini, Silvia Leanhart, Xue Jiang, Haiyan Qin, Wenbo Zhi, Stefka D Spassieva, Erhard Bieberich
We reported that amyloid beta peptide (Abeta42) activated neutral sphingomyelinase 2 (nSMase2) thereby increasing the concentration of the sphingolipid ceramide in astrocytes. Here, we show that Abeta42 induced mitochondrial fragmentation in wild type astrocytes, but not in nSMase2-deficient cells or astrocytes treated with Fumonisin B1 (FB1), an inhibitor of ceramide synthases. Unexpectedly, ceramide depletion was concurrent with rapid movements of mitochondria, indicating an unknown function of ceramide for mitochondria...
January 10, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29317070/hypothesis-for-the-cause-and-therapy-of-neurodegenerative-diseases
#15
Philip Serwer
The cause and therapy of neurodegenerative diseases remain unsolved puzzles. These diseases are correlated with presence of beta sheet-rich amyloid assemblies. Here, I derive and assemble puzzle pieces to obtain a loose end-tying hypothesis for cause with direct implications for therapy. I use the following extrapolations to find connectable puzzle pieces: (a) the traditional extrapolation that amyloid/amyloid precursors cause disease, (b) a recent extrapolation that amyloid-forming proteins, some of which are virus protein homologs, are components of an empirically obscure innate immune system that counters insults, including those by both viruses and bacteria, (c) a new extrapolation that various insults produce assemblies with structural features in common and that amyloid-forming, innate immune system proteins recognize these features and, then, counter insults by co-assembly, (d, 1) a second new extrapolation that beta sheet is a common structural feature and is extended during insult-neutralizing co-assembly and (d, 2) an appendix, derived from studies of phages T3 and T4, that most insult-produced assemblies are obscure to current biochemical analysis...
January 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29316661/iridoids-and-other-monoterpenes-in-the-alzheimer-s-brain-recent-development-and-future-prospects
#16
REVIEW
Solomon Habtemariam
Iridoids are a class of monoterpenoid compounds constructed from 10-carbon skeleton of isoprene building units. These compounds in their aglycones and glycosylated forms exist in nature to contribute to mechanisms related to plant defenses and diverse plant-animal interactions. Recent studies have also shown that iridoids and other structurally related monoterpenes display a vast array of pharmacological effects that make them potential modulators of the Alzheimer's disease (AD). This review critically evaluates the therapeutic potential of these natural products by assessing key in vitro and in vivo data published in the scientific literature...
January 7, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29315574/palmitate-induced-c-ebp-homologous-protein-activation-leads-to-nf-%C3%AE%C2%BAb-mediated-increase-in-bace1-activity-and-amyloid-beta-genesis
#17
Gurdeep Marwarha, Jared Schommer, Jonah Lund, Trevor Schommer, Othman Ghribi
The etiology of Alzheimer's disease (AD) is egregiously comprehended, but epidemiological studies have posited that diets rich in the saturated fatty acid palmitic acid (palmitate) are a significant risk factor. The production and accumulation of Amyloid-beta peptide (Aβ) is considered the core pathological molecular event in the pathogenesis of AD. The rate limiting step in Aβ genesis from Amyloid-β precursor protein (AβPP) is catalyzed by the enzyme β-site APP cleaving enzyme 1 (BACE1), the expression and enzymatic activity of which is significantly upregulated in the AD brain...
January 6, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29314823/amyloid-beta-peptide-vhhq-klvff-and-iiglmvggvv-domains-involved-in-fibrilization-afm-and-electrochemical-characterization
#18
Teodor Adrian Enache, Ana-Maria Chiorcea-Paquim, Ana Maria Oliveira-Brett
The time-dependent structural modifications and oxidation behavior of specifically chosen five short amyloid beta (Aβ) peptides, Aβ1-16, Aβ1-28, Aβ10-20, Aβ12-28, and Aβ17-42, fragments of the complete human Aβ1-40 peptide, were investigated by atomic force microscopy (AFM) and voltammetry. The objective was to determine the influence of different Aβ domains (VHHQ that contains electroactive histidine H residues, KLVFF that is the peptide hydrophobic aggregation core, and IIGLMVGGVV that is the C-terminus hydrophobic region), and of Aβ peptide hydrophobicity, in the fibrilization mechanism...
January 9, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29311632/bace1-dependent-amyloid-processing-regulates-hypothalamic-leptin-sensitivity-in-obese-mice
#19
Paul J Meakin, Susan M Jalicy, Gemma Montagut, David J P Allsop, Daniella L Cavellini, Stuart W Irvine, Christopher McGinley, Mary K Liddell, Alison D McNeilly, Karolina Parmionova, Yu-Ru Liu, Charlotte L S Bailey, J Kim Dale, Lora K Heisler, Rory J McCrimmon, Michael L J Ashford
Obesity places an enormous medical and economic burden on society. The principal driver appears to be central leptin resistance with hyperleptinemia. Accordingly, a compound that reverses or prevents leptin resistance should promote weight normalisation and improve glucose homeostasis. The protease Bace1 drives beta amyloid (Aβ) production with obesity elevating hypothalamic Bace1 activity and Aβ1-42 production. Pharmacological inhibition of Bace1 reduces body weight, improves glucose homeostasis and lowers plasma leptin in diet-induced obese (DIO) mice...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29310864/brain-amyloid-burden-and-cerebrovascular-disease-are-synergistically-associated-with-neurometabolism-in-cognitively-unimpaired-older-adults
#20
Simon J Schreiner, Thomas Kirchner, Atul Narkhede, Michael Wyss, Jiri M G Van Bergen, Stephanie C Steininger, Anton Gietl, Sandra E Leh, Valerie Treyer, Alfred Buck, Klaas P Pruessmann, Roger M Nitsch, Christoph Hock, Anke Henning, Adam M Brickman, Paul G Unschuld
Alzheimer's disease (AD) is the most common cause of cognitive dysfunction in older adults. The pathological hallmarks of AD such as beta amyloid (Aβ) aggregation and neurometabolic change, as indicated by altered myo-inositol (mI) and N-acetylaspartate (NAA) levels, typically precede the onset of cognitive dysfunction by years. Furthermore, cerebrovascular disease occurs early in AD, but the interplay between vascular and neurometabolic brain change is largely unknown. Thirty cognitively normal older adults (age = 70 ± 5...
December 12, 2017: Neurobiology of Aging
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