87,755 results match your criteria Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis[Journal]


Generation of induced pluripotent stem cells (iPSCs) IRMBi002-A from an Alzheimer's disease patient carrying a D694N mutation in the APP gene.

Stem Cell Res 2019 Apr 15;37:101438. Epub 2019 Apr 15.

Institute for Regenerative Medicine and Biotherapy (IRMB), Montpellier, France; Hopital St Eloi, CHU Montpellier, 80 rue augustin Fliche, 30295 Montpellier, France. Electronic address:

Induced pluripotent stem cells (iPSC) were generated from skin fibroblasts obtained from a 58 year-old woman suffering from Alzheimer's disease and carrying a D694N mutation on Amyloid precursor protein (APP). Fibroblasts were reprogrammed into iPSC using the integration-free Sendai Virus which allows the expression of the Yamanaka factors. Verification of their pluripotency was achieved by demonstrating the expression of pluripotency markers and their differentiation potential into the three primary germ layers. Read More

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http://dx.doi.org/10.1016/j.scr.2019.101438DOI Listing

Exendin-4 attenuates brain mitochondrial toxicity through PI3K/Akt-dependent pathway in amyloid beta (1-42)-induced cognitive deficit rats.

Neurochem Int 2019 Apr 17. Epub 2019 Apr 17.

Division of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura, 281 406, India.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss, disorientation and gradual deterioration of intellectual ability. In the pharmacotherapy of AD, the mitochondrial protective activity of Exendin-4 in experimental studies is yet to be established though its effectiveness is demonstrated in these patients. Therefore, the mitochondria protective activity of Exendin-4 (5 μg/kg, i. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S01970186193002
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http://dx.doi.org/10.1016/j.neuint.2019.04.006DOI Listing
April 2019
1 Read

A contemporary biological pathway of islet amyloid polypeptide for the management of diabetic dementia.

Chem Biol Interact 2019 Apr 17. Epub 2019 Apr 17.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney (UTS), Ultimo, NSW 2007, Australia; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute (HMRI) & School of Biomedical Sciences and Pharmacy, The University of Newcastle (UoN), Callaghan, NSW 2308, Australia. Electronic address:

Major challenges of dealing elder patients with diabetes mellitus (DM) are the individualization of consideration in persons with various comorbid types of conditions. In spite of the fact that microvascular and macrovascular problems associated with DM are well documented, there is only a few numbers of reports viewing different conditions, for example, cognitive dysfunction. Cognitive dysfunction is of specific significance due to its effect on self-care and quality of life. Read More

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http://dx.doi.org/10.1016/j.cbi.2019.04.022DOI Listing

In vitro models of synucleinopathies: informing on molecular mechanisms and protective strategies.

J Neurochem 2019 Apr 20. Epub 2019 Apr 20.

Institute of Neuroscience, The Medical School, Newcastle University, Framlington Place, Newcastle Upon Tyne, NE2 4HH, UK.

Alpha-synuclein (aSyn) is a central player in Parkinson's disease (PD) and in a spectrum of neurodegenerative diseases collectively known as synucleinopathies. The protein was first associated with PD just over 20 years ago, when it was found to (i) be a major component of Lewy bodies and, (ii) to be also associated with familial forms of PD. The characterization of aSyn pathology has been achieved through postmortem studies of human brains. Read More

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http://dx.doi.org/10.1111/jnc.14707DOI Listing
April 2019
2 Reads

LRP1 Has a Predominant Role in Production over Clearance of Aβ in a Mouse Model of Alzheimer's Disease.

Mol Neurobiol 2019 Apr 19. Epub 2019 Apr 19.

Laboratory for Experimental Mouse Genetics, Department of Human Genetics, KU Leuven, Herestraat 49, Box 604, 3000, Leuven, Belgium.

The low-density lipoprotein receptor-related protein-1 (LRP1) has a dual role in the metabolism of the amyloid precursor protein (APP). In cellular models, LRP1 enhances amyloid-β (Aβ) generation via APP internalization and thus its amyloidogenic processing. However, conditional knock-out studies in mice define LRP1 as an important mediator for the clearance of extracellular Aβ from brain via cellular degradation or transcytosis across the blood-brain barrier (BBB). Read More

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http://dx.doi.org/10.1007/s12035-019-1594-2DOI Listing

Repetitive transcranial magnetic stimulation protects mice against 6-OHDA-induced Parkinson's disease symptoms by regulating brain amyloid β level.

Mol Cell Biochem 2019 Apr 19. Epub 2019 Apr 19.

Department of Rehabilitation, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, People's Republic of China.

Repetitive transcranial magnetic stimulation (rTMS) is a technique protecting neurons against diverse neurodegenerative disorders by delivering magnetic stimuli into the brain through the intact scalp. In the current study, the protection effect of rTMS on Parkinson's disease (PD) and the associated mechanism driving the treatment were explored. The PD symptoms were induced using 6-OHDA in mice, and the effect of rTMS of two frequencies (1 Hz and 10 Hz) on the cognitive behaviors and neuron viability was detected. Read More

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http://dx.doi.org/10.1007/s11010-019-03531-wDOI Listing

α-Sheet secondary structure in amyloid β-peptide drives aggregation and toxicity in Alzheimer's disease.

Proc Natl Acad Sci U S A 2019 Apr 19. Epub 2019 Apr 19.

Department of Molecular Engineering, University of Washington, Seattle, WA 98195;

Alzheimer's disease (AD) is characterized by the deposition of β-sheet-rich, insoluble amyloid β-peptide (Aβ) plaques; however, plaque burden is not correlated with cognitive impairment in AD patients; instead, it is correlated with the presence of toxic soluble oligomers. Here, we show, by a variety of different techniques, that these Aβ oligomers adopt a nonstandard secondary structure, termed "α-sheet." These oligomers form in the lag phase of aggregation, when Aβ-associated cytotoxicity peaks, en route to forming nontoxic β-sheet fibrils. Read More

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http://dx.doi.org/10.1073/pnas.1820585116DOI Listing

Congo Red fluorescence for rapid characterization of synthetic curli systems.

Appl Environ Microbiol 2019 Apr 19. Epub 2019 Apr 19.

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, United States

Curli are amyloid proteins, assembled into extracellular polymeric fibers by bacteria during biofilm formation. The beta-sheet rich protein CsgA, the primary structural component of the fibers, is secreted through dedicated machinery, and self-assembles into cell-anchored fibers many times longer than the cell. Here, we have developed an fluorescence assay for curli production that exploits the fluorescent properties of Congo Red dye when bound to amyloid, allowing for rapid and robust curli quantification. Read More

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http://dx.doi.org/10.1128/AEM.00434-19DOI Listing

Preparation of Benzothiazolyl-Decorated Nanoliposomes.

Molecules 2019 Apr 18;24(8). Epub 2019 Apr 18.

Laboratory of Pharmaceutical Technology, Dept. of Pharmacy, School of Health Sciences, University of Patras, 26510 Rio, Greece.

Amyloid β (Aβ) species are considered as potential targets for the development of diagnostics/therapeutics towards Alzheimer's disease (AD). Nanoliposomes which are decorated with molecules having high affinity for Aβ species may be considered as potential carriers for AD theragnostics. Herein, benzothiazolyl (BTH) decorated nanoliposomes were prepared for the first time, after synthesis of a lipidic BTH derivative (lipid-BTH). Read More

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http://dx.doi.org/10.3390/molecules24081540DOI Listing

Correct partner makes the difference: Septin G-interface plays a critical role in amyloid formation.

Int J Biol Macromol 2019 Apr 16. Epub 2019 Apr 16.

Instituto de Física de São Carlos, Universidade de São Paulo, Av. João Dagnone, 1100, São Carlos, SP CEP 13563-120, Brazil. Electronic address:

Septins are members of a group of GTP-binding proteins highly conserved in eukaryotes, being linked to diverse cell processes, such as cytokinesis and membrane association. On the other hand, the malfunction of septins is linked to several pathological processes including neurodegeneration and oncogenesis. Septins interact with each other forming heterocomplexes that polymerize in filaments. Read More

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http://dx.doi.org/10.1016/j.ijbiomac.2019.04.105DOI Listing

The Upper Hand of the Otu Amyloid Fibers: Increasing Enzymatic Activity and Prolonging Lifespan.

Mol Cell 2019 Apr;74(2):225-226

Hubrecht Institute of the Royal Netherlands Academy of Arts and Sciences & University Medical Center Utrecht, Utrecht, the Netherlands; Department of Biomedical Science of Cells and Systems, University Medical Center Groningen, Groningen, the Netherlands. Electronic address:

The formation of amyloid fibers is usually associated with aging and neurodegeneration. In this issue of Molecular Cell, Ji et al. (2019) demonstrate that the deubiquitinase Otu coalesces into amyloid-like fibers to enhance its activity and ensure its optimum biological function. Read More

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http://dx.doi.org/10.1016/j.molcel.2019.03.038DOI Listing

Protein Sequence Editing of SKN-1A/Nrf1 by Peptide:N-Glycanase Controls Proteasome Gene Expression.

Cell 2019 Apr;177(3):737-750.e15

Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address:

The proteasome mediates selective protein degradation and is dynamically regulated in response to proteotoxic challenges. SKN-1A/Nrf1, an endoplasmic reticulum (ER)-associated transcription factor that undergoes N-linked glycosylation, serves as a sensor of proteasome dysfunction and triggers compensatory upregulation of proteasome subunit genes. Here, we show that the PNG-1/NGLY1 peptide:N-glycanase edits the sequence of SKN-1A protein by converting particular N-glycosylated asparagine residues to aspartic acid. Read More

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http://dx.doi.org/10.1016/j.cell.2019.03.035DOI Listing

Cold Thermal Response of an Amyloid Oligomer Differs from Typical Globular Protein Cold Denaturation.

J Phys Chem Lett 2019 Apr 19. Epub 2019 Apr 19.

In contrast with the general behavior of folded proteins, cold thermal response of amyloid assemblies is difficult to elicit with simple models. We exploit exhaustive simulations to evaluate the thermal response of a barrel-shaped model amyloid oligomer, with a distinct hydrophobic core akin to that of folded proteins. Cumulative thermal data over 210 to 483 K indicate a sharp inflexion and rise in structural stability as the temperature is lowered below the melting temperature of the water model. Read More

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http://dx.doi.org/10.1021/acs.jpclett.9b00709DOI Listing

Knockout of apolipoprotein A-I decreases parenchymal and vascular β-amyloid pathology in the Tg2576 mouse model of Alzheimer's disease.

Neuropathol Appl Neurobiol 2019 Apr 19. Epub 2019 Apr 19.

School of Life, Health and Chemical Sciences, STEM Faculty, The Open University, Milton Keynes, UK.

Aims: Apolipoprotein A-I (apoA-I), the principal apolipoprotein associated with high density lipoproteins (HDL) in the periphery, is also found at high concentrations in the cerebrospinal fluid. Previous studies have reported either no impact or vascular-specific effects of apoA-I knockout on β-amyloid (Aβ) pathology. However, the putative mechanism(s) by which apoA-I may influence Aβ deposition is unknown. Read More

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http://dx.doi.org/10.1111/nan.12556DOI Listing
April 2019
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Neuroprotective Effects of Zafirlukast, Piracetam and Their Combination on L-Methionine-Induced Vascular Dementia in Rats.

Fundam Clin Pharmacol 2019 Apr 18. Epub 2019 Apr 18.

Pharmacology Department, October University for Modern Science and Arts, 11787, 6, October City, Egypt.

Vascular dementia is considered a vascular cognitive impairment disease caused by neuronal degeneration in the brain. Several studies have supported the hypothesis that oxidative stress and endothelial dysfunction are the main pathogenic factors in vascular dementia. This current study aims to determine the possible neuroprotective effects of zafirlukast, piracetam and the combination of piracetam and zafirlukast on L-methionine-induced vascular dementia in rats. Read More

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http://dx.doi.org/10.1111/fcp.12473DOI Listing

Solubilizing Trityl-type Tag to Synthesize Asx/Glx-containing Peptides.

Chembiochem 2019 Apr 18. Epub 2019 Apr 18.

Peptide Institute, Inc., SAITO Research Center, 7-2-9 Saito-Asagi, 5670085, Ibaraki-shi, JAPAN.

A novel solubilizing tag system for Asp/Asn/Glu/Gln-containing peptides is described. In this method, an Asp/Glu[Dbz-Cys-NH2]-containing peptide (Dbz: 3,4-diaminobenzoic acid) is first synthesized by Fmoc solid-phase peptide synthesis. The solubilizing moiety containing an oligo-Lys group is then attached to the peptide in hexafluoroisopropanol solution via a trityl anchor to afford a hydrophilic tagged peptide. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/cbic.2019001
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http://dx.doi.org/10.1002/cbic.201900193DOI Listing
April 2019
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Comparative analyses of plasma amyloid-β levels in heterogeneous and monomerized states by interdigitated microelectrode sensor system.

Sci Adv 2019 Apr 17;5(4):eaav1388. Epub 2019 Apr 17.

Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.

Detection of amyloid-β (Aβ) aggregates contributes to the diagnosis of Alzheimer disease (AD). Plasma Aβ is deemed a less invasive and more accessible hallmark of AD, as Aβ can penetrate blood-brain barriers. However, correlations between biofluidic Aβ concentrations and AD progression has been tenuous. Read More

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http://dx.doi.org/10.1126/sciadv.aav1388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469948PMC

Secondary nucleation and elongation occur at different sites on Alzheimer's amyloid-β aggregates.

Sci Adv 2019 Apr 17;5(4):eaau3112. Epub 2019 Apr 17.

Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.

The aggregates of the Aβ peptide associated with Alzheimer's disease are able to both grow in size as well as generate, through secondary nucleation, new small oligomeric species, that are major cytotoxins associated with neuronal death. Despite the importance of these amyloid fibril-dependent processes, their structural and molecular underpinnings have remained challenging to elucidate. Here, we consider two molecular chaperones: the Brichos domain, which suppresses specifically secondary nucleation processes, and clusterin which our results show is capable of inhibiting, specifically, the elongation of Aβ fibrils at remarkably low substoichiometric ratios. Read More

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http://dx.doi.org/10.1126/sciadv.aau3112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469941PMC
April 2019
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Contributions of Animal Models to the Mechanisms and Therapies of Transthyretin Amyloidosis.

Front Physiol 2019 2;10:338. Epub 2019 Apr 2.

Institute of Brain Science, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

Transthyretin amyloidosis (ATTR amyloidosis) is a fatal systemic disease caused by amyloid deposits of misfolded transthyretin, leading to familial amyloid polyneuropathy and/or cardiomyopathy, or a rare oculoleptomeningeal amyloidosis. A good model system that mimic the disease phenotype is crucial for the development of drugs and treatments for this devastating degenerative disorder. The present models using fruit flies, worms, rodents, non-human primates and induced pluripotent stem cells have helped researchers understand important disease-related mechanisms and test potential therapeutic options. Read More

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http://dx.doi.org/10.3389/fphys.2019.00338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454033PMC
April 2019
2 Reads

Age, but Not Amyloidosis, Induced Changes in Global Levels of Histone Modifications in Susceptible and Disease-Resistant Neurons in Alzheimer's Disease Model Mice.

Front Aging Neurosci 2019 3;11:68. Epub 2019 Apr 3.

Wicking Dementia Research and Education Centre, College of Health and Medicine, University of Tasmania, Hobart, TAS, Australia.

There is increasing interest in the role of epigenetic alterations in Alzheimer's disease (AD). The epigenome of every cell type is distinct, yet data regarding epigenetic change in specific cell types in aging and AD is limited. We investigated histone tail modifications in neuronal subtypes in wild-type and APP/PS1 mice at 3 (pre-pathology), 6 (pathology-onset) and 12 (pathology-rich) months of age. Read More

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http://dx.doi.org/10.3389/fnagi.2019.00068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456813PMC
April 2019
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Icariin Attenuates M1 Activation of Microglia and Aβ Plaque Accumulation in the Hippocampus and Prefrontal Cortex by Up-Regulating PPARγ in Restraint/Isolation-Stressed APP/PS1 Mice.

Front Neurosci 2019 28;13:291. Epub 2019 Mar 28.

Department of Neurology, Jinan Central Hospital, Shandong University, Jinan, China.

Background: Studies have shown that psychosocial stress is involved in Alzheimer's disease (AD) pathogenesis; it induces M1 microglia polarization and production of pro-inflammatory cytokines, leading to neurotoxic outcomes and decreased β-amyloid (Aβ) clearance. Icariin has been proven to be an effective anti-inflammatory agent and to activate peroxisome proliferator-activated receptors gamma (PPARγ) which induces the M2 phenotype in the microglia. However, whether restraint/isolation stress reduces the clearance ability of microglia by priming and polarizing microglia to the M1 phenotype, and the effects of icariin in attenuating the inflammatory response and relieving the pathological changes of AD are still unclear. Read More

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http://dx.doi.org/10.3389/fnins.2019.00291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6455051PMC

Nitazoxanide, an anti-parasitic drug, efficiently ameliorates learning and memory impairments in AD model mice.

Acta Pharmacol Sin 2019 Apr 18. Epub 2019 Apr 18.

Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

The pathogenesis of Alzheimer's disease (AD) is characterized by both accumulation of β-amyloid (Aβ) plaque and formation of neurofibrillary tangles in the brain. Recent evidence shows that autophagy activation may potently promote intracellular Aβ clearance. Thus targeting autophagy becomes a promising strategy for discovery of drug leads against AD. Read More

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http://dx.doi.org/10.1038/s41401-019-0220-1DOI Listing

Hydrophobicity and aggregation, but not glycation, are key determinants for uptake of thermally processed β-lactoglobulin by THP-1 macrophages.

Food Res Int 2019 Jun 22;120:102-113. Epub 2019 Jan 22.

Food and Biobased Research, Wageningen University and Research, P.O.Box 17, 6700 AA Wageningen, The Netherlands; Laboratory of Food Chemistry, Wageningen University and Research, Wageningen, The Netherlands. Electronic address:

The aim of this study is to investigate the immunological relevance of modifications of food protein structure due to thermal processing. We investigated the uptake of β-lactoglobulin, treated with 3 different processing methods, by THP-1 macrophages: wet heating (60 °C in solution) and high- or low-temperature (130 °C or 50 °C, respectively) dry heating, combined with either of 8 types of saccharides or without saccharide. The processing method that was applied significantly affected the uptake of BLG by THP-1 macrophages, while the type of saccharide only had an influence in high-temperature dry heated samples. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09639969193003
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http://dx.doi.org/10.1016/j.foodres.2019.01.038DOI Listing
June 2019
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Non-conventional compounds with potential therapeutic effects against Alzheimer's disease.

Expert Rev Neurother 2019 Apr 19. Epub 2019 Apr 19.

a Laboratory of Molecular Modeling, Department of Chemistry , Federal University of Lavras , Lavras/MG , 37200-000 , Brazil.

Introduction: Alzheimer's disease (AD) is the most common cause of dementia. Clinical progress in this pathogenesis field has drawn the attention of researchers, stimulating the investigation of novel treatment methods. Current therapies that deal with cholinesterase inhibitors and/or NMDA antagonists have shown a modest symptomatic potential, increasing the need for research into more efficient therapeutics. Read More

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http://dx.doi.org/10.1080/14737175.2019.1608823DOI Listing
April 2019
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Rapid fragmentation during seeded lysozyme aggregation revealed at the single molecule level.

Anal Chem 2019 Apr 19. Epub 2019 Apr 19.

Protein aggregation is associated with neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. The poorly understood pathogenic mechanism of amyloid diseases makes early-stage diagnostics or therapeutic intervention a challenge. Seeded polymerisation that reduces the duration of the lag phase and accelerates fibril growth is a widespread model to study amyloid formation. Read More

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http://pubs.acs.org/doi/10.1021/acs.analchem.9b01221
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http://dx.doi.org/10.1021/acs.analchem.9b01221DOI Listing
April 2019
2 Reads

Natural Products in Alzheimer's Disease Therapy: Would Old Therapeutic Approaches Fix the Broken Promise of Modern Medicines?

Molecules 2019 Apr 17;24(8). Epub 2019 Apr 17.

Pharmacognosy Research Laboratories & Herbal Analysis Services UK, University of Greenwich, Central Avenue, Chatham-Maritime, Kent ME4 4TB, UK.

Despite extensive progress in understanding the pathology of Alzheimer's disease (AD) over the last 50 years, clinical trials based on the amyloid-beta (Aβ) hypothesis have kept failing in late stage human trials. As a result, just four old drugs of limited clinical outcomes and numerous side effects are currently used for AD therapy. This article assesses the common pharmacological targets and therapeutic principles for current and future drugs. Read More

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http://dx.doi.org/10.3390/molecules24081519DOI Listing
April 2019
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Altered dynamics may drift pathological fibrillization in membraneless organelles.

Biochim Biophys Acta Proteins Proteom 2019 Apr 15. Epub 2019 Apr 15.

MTA-DE Laboratory of Protein Dynamics, University of Debrecen, Hungary. Electronic address:

Protein phase transition can generate non-membrane bound cellular compartments, which can convert from liquid-like to solid-like states. While the molecular driving forces of phase separation have been largely understood, much less is known about the mechanisms of material-state conversion. We apply a recently developed algorithm to describe the weak interaction network of multivalent motifs, and simulate the effect of pathological mutations. Read More

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http://dx.doi.org/10.1016/j.bbapap.2019.04.005DOI Listing

Intravenous Infusion of Mesenchymal Stem Cells Improves Impaired Cognitive Function in a Cerebral Small Vessel Disease Model.

Neuroscience 2019 Apr 15. Epub 2019 Apr 15.

Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan; Department of Neurology, Yale University School of Medicine, New Haven, CT, 06510, USA; Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT, 06516, USA.

Cerebral small vessel disease (CSVD) is not only a cause of vascular dementia (VD) but also a contributing factor to Alzheimer's disease (AD). The essential pathological feature of CSVD is the disruption of blood-brain barrier (BBB). Dysfunction of BBB due to degeneration of both endothelial cells and pericytes in capillaries leads to neuronal damage and progressive brain atrophy. Read More

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http://dx.doi.org/10.1016/j.neuroscience.2019.04.018DOI Listing

Impaired dynamic cerebral autoregulation in patients with cerebral amyloid angiopathy.

Brain Res 2019 Apr 15. Epub 2019 Apr 15.

Department of Neuroradiology, University Medical Center Freiburg, Germany.

Cerebral amyloid angiopathy (CAA) might disturb the sensitive mechanism of cerebral pressure autoregulation. This study examines whether dynamic cerebral autoregulation (CA) is impaired in the posterior or anterior circulation of CAA patients. Fifteen patients with known CAA on magnetic resonance imaging (MRI) and 14 age-matched controls were examined with transcranial Doppler. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00068993193020
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http://dx.doi.org/10.1016/j.brainres.2019.04.014DOI Listing
April 2019
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In silico analysis of the V66M variant of human BDNF in psychiatric disorders: An approach to precision medicine.

PLoS One 2019 18;14(4):e0215508. Epub 2019 Apr 18.

Department of Genetics and Molecular Biology, Bioinformatics and Computational Biology Laboratory, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro, Rio de Janeiro, Brazil.

Brain-derived neurotrophic factor (BDNF) plays an important role in neurogenesis and synapse formation. The V66M is the most prevalent BDNF mutation in humans and impairs the function and distribution of BDNF. This mutation is related to several psychiatric disorders. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215508PLOS

Posttranslational modifications and proteinopathies: how guardians of the proteome are defeated.

Authors:
Heidi Olzscha

Biol Chem 2018 Dec 1. Epub 2018 Dec 1.

Institut für Physiologische Chemie, Medizinische Fakultät, Martin-Luther-Universität Halle- Wittenberg, Hollystr. 1, D-06114 Halle/Saale, Germany.

Protein folding is one of the fundamental processes in life, and therefore needs to be tightly regulated. Many cellular quality control systems are in place to ensure that proteostasis is optimally adjusted for a changing environment, facilitating protein folding, translocation and degradation. These systems include the molecular chaperones and the major protein degradation systems, namely the ubiquitin proteasome system and autophagy. Read More

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http://dx.doi.org/10.1515/hsz-2018-0458DOI Listing
December 2018

Glutamine side chain 13C=18O as a non-perturbative IR probe of amyloid fibril hydration and assembly.

J Am Chem Soc 2019 Apr 17. Epub 2019 Apr 17.

Infrared (IR) spectroscopy has provided considerable insights into the structures, dynamics, and formation mechanisms of amyloid fibrils. IR probes, such as main chain 13C=18O, have been widely employed to obtain site-specific structural information, yet only secondary structures and strand-to-strand arrangements can be probed. Very few non-perturbative IR probes are available to report on side chain conformation and environments, which are critical to determining sheet-to-sheet arrangements in steric zippers within amyloids. Read More

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http://dx.doi.org/10.1021/jacs.9b00577DOI Listing

Herpesviral infections and antimicrobial protection for Alzheimer's disease: Implications for prevention and treatment.

Authors:
Qingsong Qin Yun Li

J Med Virol 2019 Apr 17. Epub 2019 Apr 17.

Sleep Medicine Center, Shantou University Medical College, Shantou, Guangdong, China.

Accumulating evidence suggests that infections by herpesviruses might be closely linked to Alzheimer's disease (AD). Pathological hallmarks of AD brains include senile plaques induced by amyloid β peptide (Aβ) in the extracellular space and intracellular neurofibrillary tangles (NFTs) consisting of phosphorylated tau protein. The prevailing hypothesis for the mechanism of AD is amyloid cascade reaction. Read More

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http://dx.doi.org/10.1002/jmv.25481DOI Listing
April 2019
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Ubiquitin binds the amyloid β peptide and interferes with its clearance pathways.

Chem Sci 2019 Mar 10;10(9):2732-2742. Epub 2019 Jan 10.

Consiglio Nazionale delle Ricerche , Istituto di Biostrutture e Bioimmagini , Via P. Gaifami 18 , 95126 Catania , Italy . Email:

Several lines of evidence point to a compromised proteostasis associated with a reduction of the Ubiquitin Proteasome System (UPS) activity in patients affected by Alzheimer's Disease (AD) and suggest that the amyloid β peptide (Aβ) is an important player in the game. Inspired also by many reports, underlining the presence of ubiquitin (Ub) in the amyloid plaques of AD brains, here we set out to test whether Ub may bind the Aβ peptide and have any effect on its clearance pathways. By using an integrated array of MALDI-TOF/UPLC-HRMS, fluorescence, NMR, SPR, Microscale Thermophoresis (MST) and molecular dynamics studies, we consistently demonstrated that Aβ40 binds Ub with a 1 : 1 stoichiometry and in the high micromolar range. Read More

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http://xlink.rsc.org/?DOI=C8SC03394C
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http://dx.doi.org/10.1039/c8sc03394cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419943PMC
March 2019
1 Read

Mechanisms of Metabolite Amyloid Formation: Computational Studies for Drug Design against Metabolic Disorders.

ACS Med Chem Lett 2019 Apr 15;10(4):666-670. Epub 2019 Feb 15.

Istituto di Chimica del Riconoscimento Molecolare, CNR, via Mario Bianco 9, Milano 20131, Italy.

Ordered self-organization of polypeptides into fibrillar assemblies has been associated with a number of pathological conditions linked to degenerative diseases. Recent experimental observations have demonstrated that even small-molecule metabolites can aggregate into supramolecular arrangements with structural and functional properties reminiscent of peptide-based amyloids. The molecular determinants of such mechanisms, however, are not clear yet. Read More

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http://dx.doi.org/10.1021/acsmedchemlett.9b00024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466829PMC
April 2019
2 Reads

Surveillance of amyloidosis in stranded and bycaught cetaceans off Hokkaido, Japan.

J Vet Med Sci 2019 Apr 17. Epub 2019 Apr 17.

Laboratory of Veterinary Pathology, Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine.

Systemic amyloidosis is rarely reported among cetaceans, and a surveillance dedicated for its occurrence across a certain geographic location has not been reported. Between 2013 and 2018, comprehensive gross and histopathologic examinations were conducted on 54 animals comprising 11 species of stranded and bycaught cetaceans in Hokkaido, Japan. Systemic amyloidosis was diagnosed in 2 out of 3 Stejneger's beaked whales (Mesoplodon stejnegeri), through Congo red staining and immunohistochemistry for amyloid A. Read More

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http://dx.doi.org/10.1292/jvms.18-0706DOI Listing

Site-specific glycations of Aβ1-42 affect fibril formation and are neurotoxic.

J Biol Chem 2019 Apr 17. Epub 2019 Apr 17.

University of Auckland, New Zealand.

Amyloid β1-42 (Aβ1-42) peptide is involved in Alzheimer's disease (AD) pathogenesis and is prone to glycation, an irreversible process resulting in proteins with accumulated advanced glycated end products (AGEs). Nε-(carboxyethyl)lysine (CEL) is a common AD-associated AGE, occurring at either Lys-16 or Lys-28 of Aβ1-42. Methylglyoxal is commonly used for the unspecific glycation of Aβ1-42, which results in a complex mixture of AGE-modified peptides and makes interpretation of a causative AGE at a specific amino acid residue difficult. Read More

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http://www.jbc.org/lookup/doi/10.1074/jbc.RA118.006846
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http://dx.doi.org/10.1074/jbc.RA118.006846DOI Listing
April 2019
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Extracellular matrix components modulate different stages in β2-microglobulin amyloid formation.

J Biol Chem 2019 Apr 17. Epub 2019 Apr 17.

University of Leeds, United Kingdom.

Amyloid deposition of wild-type human β2-microglobulin (WT-hβ2m) in the joints of long-term hemodialysis patients is the hallmark of dialysis-related amyloidosis (DRA). In vitro, WT-hβ2m does not form amyloid fibrils at physiological pH and temperature unless co-solvents or other reagents are added. Therefore, understanding how fibril formation is initiated and maintained in the joint space is important for elucidating WT-hβ2m aggregation and DRA onset. Read More

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http://www.jbc.org/lookup/doi/10.1074/jbc.RA119.008300
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http://dx.doi.org/10.1074/jbc.RA119.008300DOI Listing
April 2019
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Fibril self-assembly of amyloid-spider silk block polypeptides.

Biomacromolecules 2019 Apr 17. Epub 2019 Apr 17.

Due to their association with debilitating diseases and their potential applications in developing novel bionanomaterials, highly ordered amyloid fibrils have recently received considerable attention. While many studies have thus far focused on amyloid fibrils made with short peptides containing just one steric zipper-forming segment of native amyloid proteins, the self-assembly of proteins containing multiple steric zipper-forming segments has been rarely explored. Here we develop a strategy to create four block polypeptides, each containing 16 repeats of a zipper-forming segment from four different amyloid morphological classes. Read More

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http://dx.doi.org/10.1021/acs.biomac.9b00218DOI Listing

Impact of Amyloid Polymorphism on Prion-Chaperone Interactions in Yeast.

Viruses 2019 Apr 16;11(4). Epub 2019 Apr 16.

Department of Chemistry, Lafayette College, Easton, PA 18042, USA.

Yeast prions are protein-based genetic elements found in the baker's yeast , most of which are amyloid aggregates that propagate by fragmentation and spreading of small, self-templating pieces called propagons. Fragmentation is carried out by molecular chaperones, specifically Hsp104, Hsp70, and Hsp40. Like other amyloid-forming proteins, amyloid-based yeast prions exhibit structural polymorphisms, termed "strains" in mammalian systems and "variants" in yeast, which demonstrate diverse phenotypes and chaperone requirements for propagation. Read More

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http://dx.doi.org/10.3390/v11040349DOI Listing

Oleuropein aglycone and hydroxytyrosol interfere differently with toxic Aβ aggregation.

Food Chem Toxicol 2019 Apr 14. Epub 2019 Apr 14.

Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio', University of Florence, Viale Morgagni 50 - 50134, Florence, Italy; Interuniversity Center for the Study of Neurodegenerative Diseases (CIMN), Florence, Italy. Electronic address:

Oleuropein aglycone (OleA), the most abundant polyphenol in extra virgin olive oil (EVOO), and Hydroxythyrosol (HT), the OleA main metabolite, have attracted our interest due to their multitarget effects, including the interference with amyloid aggregation path. However, the mechanistic details of their anti-amyloid effect are not known yet. We report here a broad biophysical approach and cell biology techniques that enabled us to characterize the different molecular mechanisms by which OleA and HT modulate the Aβ fibrillation, a main histopathological feature of Alzheimer's disease (AD). Read More

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http://dx.doi.org/10.1016/j.fct.2019.04.015DOI Listing
April 2019
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Simultaneous Live Imaging of Multiple Endogenous Proteins Reveals a Mechanism for Alzheimer's-Related Plasticity Impairment.

Cell Rep 2019 Apr;27(3):658-665.e4

Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Program in Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address:

CaMKIIα is a central mediator of bidirectional synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD). To study how CaMKIIα movement during plasticity is affected by soluble amyloid-β peptide oligomers (Aβ), we used FingR intrabodies to simultaneously image endogenous CaMKIIα and markers for excitatory versus inhibitory synapses in live neurons. Aβ blocks LTP-stimulus-induced CaMKIIα accumulation at excitatory synapses. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.041DOI Listing

Strength training and running elicit different neuroprotective outcomes in a β-amyloid peptide-mediated Alzheimer's disease model.

Physiol Behav 2019 Apr 14. Epub 2019 Apr 14.

Applied Neuromechanics Group, Federal University of Pampa, Uruguaiana, 97501-970, Brazil. Electronic address:

Aerobic exercise induces neuroprotection, but few studies investigated whether strength training has similar potential. Here we examine whether effects of strength training differ from those of running training concerning cognitive symptomatology, oxidative stress and cholinergic status in a model of AD-like cognitive impairment induced by intrahippocampal infusion of a mix of β-amyloid peptides (Aβ) in rats. Male Wistar rats were submitted to 8 weeks of running exercise (RunEx; 40 min sessions at 70% of indirect VO max, 3 times/week) or strength exercise (StrEx; 3 sessions/week, 12 repetitions in 8 sets, 2 sets with repetitions at 50%, 2 at 75%, 2 at 90% and 2 at 100% of the maximum load), followed by Aβ infusion in the dorsal hippocampus. Read More

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http://dx.doi.org/10.1016/j.physbeh.2019.04.012DOI Listing
April 2019
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Towards salivary C-reactive protein as a viable biomarker of systemic inflammation.

Clin Biochem 2019 Apr 14. Epub 2019 Apr 14.

Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4RN, UK. Electronic address:

C-reactive protein (CRP) is a commonly used marker of systemic inflammation, routinely measured in serum blood samples. However salivary samples offer a non-invasive and easily accessible alternative which would improve point of care (POC) testing for inflammation. Two major challenges restrict the use of saliva: the influence of the oral environment on CRP and its local production; and collecting a standardised sample given patient-dependent salivary flow rates. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00099120183091
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http://dx.doi.org/10.1016/j.clinbiochem.2019.04.006DOI Listing
April 2019
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Using Turmeric Oil as a Solvent Improves the Distribution of Sesamin-Sesamolin in the Serum and Brain of Mice.

Lipids 2019 Apr 17. Epub 2019 Apr 17.

Department of Applied Biological Chemistry, Faculty of Agriculture, Kindai University, 204-3327 Nakamachi, Nara City, Nara, 631-8505, Japan.

Accumulation of amyloid-β peptide is associated with Alzheimer's dementia. Previously, we reported that sesamin and sesamolin inhibited β-secretase activity in vitro, and each was transported to the serum and brain in mice after oral administration. However, the bioavailability of sesamin and sesamolin was poor in mice. Read More

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http://dx.doi.org/10.1002/lipd.12147DOI Listing

Preparation and Characterization of Curcumin-Loaded Polymeric Nanomicelles to Interference with Amyloidogenesis through Glycation Method.

Biotechnol Appl Biochem 2019 Apr 16. Epub 2019 Apr 16.

Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), P.O. Box 14155-4777, Tehran, Iran.

Amyloid fibrils, including β-amyloid (Aβ) fibrils, are protein aggregates that form under certain conditions, associated with neurodegeneration that interfere with neural synaptic transmission resulting in some neural disorders, such as Alzheimer disease. The aim of this study is to inhibit amyloidogenesis by using preparatory polymeric nanomicelles as therapeutic agents and also as nano carriers for curcumin to target Aβ fibrils through the glycation method of Bovine Serum Albumin (BSA) in the presence of Phosphate Buffer Saline (PBS). Polymeric nanomicelles were prepared from Phosphatidylethanolamine-distearoyl methoxypolyethylene glycol conjugates in the presence and absence of Curcumin and then the morphological and structural characteristics of the nanomicelles were characterized in detail. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/bab.1751
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http://dx.doi.org/10.1002/bab.1751DOI Listing
April 2019
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RNA recognition motifs of disease-linked RNA-binding proteins contribute to amyloid formation.

Sci Rep 2019 Apr 16;9(1):6171. Epub 2019 Apr 16.

Molecular and Cell Biology, Taiwan International Graduate Program, Academia Sinica and Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.

Aberrant expression, dysfunction and particularly aggregation of a group of RNA-binding proteins, including TDP-43, FUS and RBM45, are associated with neurological disorders. These three disease-linked RNA-binding proteins all contain at least one RNA recognition motif (RRM). However, it is not clear if these RRMs contribute to their aggregation-prone character. Read More

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http://www.nature.com/articles/s41598-019-42367-8
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http://dx.doi.org/10.1038/s41598-019-42367-8DOI Listing
April 2019
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The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory.

Nat Commun 2019 Apr 16;10(1):1766. Epub 2019 Apr 16.

Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Feodor-Lynen Straße 17, 81377, Munich, Germany.

The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer's disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is mediated by increased tau pathology but whether rs744373 is associated with increased tau pathology in vivo is unknown. Read More

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http://www.nature.com/articles/s41467-019-09564-5
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http://dx.doi.org/10.1038/s41467-019-09564-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467911PMC
April 2019
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Ultrastructural evidence of microglial heterogeneity in Alzheimer's disease amyloid pathology.

J Neuroinflammation 2019 Apr 16;16(1):87. Epub 2019 Apr 16.

Axe neurosciences, Centre de recherche du CHU de Québec-Université Laval, 2705, boulevard Laurier, T2-50, Quebec, QC, G1V 4G2, Canada.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by the deposition of extracellular fibrillar amyloid β (fΑβ) and the intracellular accumulation of neurofibrillary tangles. As AD progresses, Aβ drives a robust and prolonged inflammatory response via its recognition by microglia, the brain's immune cells. Microglial reactivity to fAβ plaques may impair their normal surveillance duties, facilitating synaptic loss and neuronal death, as well as cognitive decline in AD. Read More

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http://dx.doi.org/10.1186/s12974-019-1473-9DOI Listing
April 2019
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Plasmalogens and Alzheimer's disease: a review.

Lipids Health Dis 2019 Apr 16;18(1):100. Epub 2019 Apr 16.

Faculty of Health, Deakin University, Geelong, VIC, 3217, Australia.

Growing evidence suggests that ethanolamine plasmalogens (PlsEtns), a subtype of phospholipids, have a close association with Alzheimer's disease (AD). Decreased levels of PlsEtns have been commonly found in AD patients, and were correlated with cognition deficit and severity of disease. Limited studies showed positive therapeutic outcomes with plasmalogens interventions in AD subjects and in rodents. Read More

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http://dx.doi.org/10.1186/s12944-019-1044-1DOI Listing