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https://www.readbyqxmd.com/read/29154879/perillyl-alcohol-alleviates-amyloid-%C3%AE-peptides-induced-mitochondrial-dysfunction-and-cytotoxicity-in-sh-sy5y-cells
#1
Mohammad Faraz Zafeer, Fakiha Firdaus, Faraz Ahmad, Rizwan Ullah, Ehraz Anis, Mohd Waseem, Asif Ali, Mohammad Mobarak Hossain
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common type of dementia in elderly ( >65years of age). Excessive extra cellular deposits of amyloid beta (Aβ) are a pathological feature of AD. Aβ can cause cell death through oxidative damage; recent studies have implicated opening of mPTP as a detrimental event in AD-related mitochondrial dysfunctions. Over the past few years, natural compounds with antioxidant properties have shown promise for intervention in AD.
November 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29154274/cognitive-decline-in-preclinical-alzheimer-s-disease-amyloid-beta-versus-tauopathy
#2
Colin M Huber, Connor Yee, Taylor May, Apoorva Dhanala, Cassie S Mitchell
 We perform a large-scale meta-analysis of 51 peer-reviewed 3xTg-AD mouse publications to compare Alzheimer's disease (AD) quantitative clinical outcome measures, including amyloid-β (Aβ), total tau, and phosphorylated tau (pTau), with cognitive performance in Morris water maze (MWM) and Novel Object Recognition (NOR). "High" levels of Aβ (Aβ40, Aβ42) showed significant but weak trends with cognitive decline (MWM: slope = 0.336, R2 = 0.149, n = 259, p < 0.001; NOR: slope = 0.156, R2 = 0...
November 14, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29151990/robot-embodied-neuronal-networks-as-an-interactive-model-of-learning
#3
Abraham M Shultz, Sangmook Lee, Mary Guaraldi, Thomas B Shea, Holly C Yanco
Background and Objective: The reductionist approach of neuronal cell culture has been useful for analyses of synaptic signaling. Murine cortical neurons in culture spontaneously form an ex vivo network capable of transmitting complex signals, and have been useful for analyses of several fundamental aspects of neuronal development hitherto difficult to clarify in situ. However, these networks lack the ability to receive and respond to sensory input from the environment as do neurons in vivo...
2017: Open Neurology Journal
https://www.readbyqxmd.com/read/29150992/accelerated-aging-and-aging-process-in-the-brain
#4
Nickolay K Isaev, Elisaveta E Genrikhs, Maria V Oborina, Elena V Stelmashook
One of the approaches to the research of the problem of aging is the study of genetic pathologies leading to accelerated aging, such as the Hutchinson-Gilford progeria syndrome, Werner syndrome, and Down syndrome. Probably, this approach can be used in an attempt to understand the neuronal mechanisms underlying normal and pathological brain aging. The analysis of the current state of scientific knowledge about these pathologies shows that in the Hutchinson-Gilford progeria and Werner syndrome, the rate of brain aging is significantly lower than the rate of whole body aging, whereas in Down syndrome, the brain ages faster than other organs due to amyloid-beta accumulation and chronic oxidative stress in the brain tissue...
November 18, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29150274/neuroprotective-potential-of-high-dose-biotin
#5
Mark F McCarty, James J DiNicolantonio
A recent controlled trial has established that high-dose biotin supplementation - 100 mg, three times daily - has a stabilizing effect on progression of multiple sclerosis (MS). Although this effect has been attributed to an optimization of biotin's essential cofactor role in the brain, a case can be made that direct stimulation of soluble guanylate cyclase (sGC) by pharmacological concentrations of biotin plays a key role in this regard. The utility of high-dose biotin in MS might reflect an anti-inflammatory effect of cGMP on the cerebral microvasculature, as well on oligodendrocyte differentiation and on Schwann cell production of neurotrophic factors thought to have potential for managing MS...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29149631/prostaglandin-j2-promotes-o-glcnacylation-raising-app-processing-by-%C3%AE-and-%C3%AE-secretases-relevance-to-alzheimer-s-disease
#6
Teneka Jean-Louis, Patricia Rockwell, Maria E Figueiredo-Pereira
Regulation of the amyloid precursor protein (APP) processing by α- and β-secretases is of special interest to Alzheimer's disease (AD), as these proteases prevent or mediate amyloid beta formation, respectively. Neuroinflammation is also implicated in AD. Our data demonstrate that the endogenous mediator of inflammation prostaglandin J2 (PGJ2) promotes full-length APP (FL-APP) processing by α- and β-secretases. The decrease in FL-APP was independent of proteasomal, lysosomal, calpain, caspase, and γ-secretase activities...
November 14, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29146293/andrographolide-a-promising-therapeutic-agent-negatively-regulates-glial-cell-derived-neurodegeneration-of-prefrontal-cortex-hippocampus-and-working-memory-impairment
#7
Sudeshna Das, K P Mishra, Lilly Ganju, S B Singh
Over activation of glial cell derived innate immune factors induces neuro-inflammation that results in neurodegenerative disease, like working memory impairment. In this study, we have investigated the role of andrographolide, a major constituent of Andrographis paniculata plant, in reduction of reactive glial cell derived working memory impairment. Real time PCR, Western bloting, flow cytometric and immunofluorescence studies demonstrated that andrographolide inhibited lipopolysaccharide (LPS)-induced overexpression of HMGB1, TLR4, NFκB, COX-2, iNOS, and release of inflammatory mediators in primary mix glial culture, adult mice prefrontal cortex and hippocampus region...
November 8, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29143445/glycyrrhiza-uralensis-and-semilicoisoflavone-b-reduce-a%C3%AE-secretion-by-increasing-ppar%C3%AE-expression-and-inhibiting-stat3-phosphorylation-to-inhibit-bace1-expression
#8
Ming-Yao Gu, Yoon Sun Chun, Dong Zhao, Ryu Shi Yong, Hyun Ok Yang
SCOPE: Glycyrrhiza uralensis extract (GUE) has been reported to improve amyloid beta (Aβ) induced cognitive deficits in mice. However, the mechanisms underlying this effect and the components involved have not been previously explored. Extracellular Aβ plaques are one of the major pathological hallmarks of Alzheimer's disease (AD). Therefore, decreasing Aβ levels is one strategy for preventing the etiology of AD. This study aimed to test the effect of GUE and semilicoisoflavone B (SB) on Aβ secretion and investigate the mechanism underlying this effect...
November 16, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29142509/using-an-nmr-metabolomics-approach-to-investigate-the-pathogenicity-of-amyloid-beta-and-alpha-synuclein
#9
M M Phelan, E Caamaño-Gutiérrez, M S Gant, R X Grosman, J Madine
Introduction: The pathogenicity at differing points along the aggregation pathway of many fibril-forming proteins associated with neurodegenerative diseases is unclear. Understanding the effect of different aggregation states of these proteins on cellular processes is essential to enhance understanding of diseases and provide future options for diagnosis and therapeutic intervention. Objectives: To establish a robust method to probe the metabolic changes of neuronal cells and use it to monitor cellular response to challenge with three amyloidogenic proteins associated with neurodegenerative diseases in different aggregation states...
2017: Metabolomics: Official Journal of the Metabolomic Society
https://www.readbyqxmd.com/read/29142396/antioxidant-and-cholinesterase-inhibitory-activities-of-ethyl-acetate-extract-of-terminalia-chebula-cell-free-in-vitro-and-in-silico-studies
#10
Mohamed Asik Rajmohamed, Suganthy Natarajan, Premkumar Palanisamy, Akbarsha Mohammad Abdulkader, Archunan Govindaraju
Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder clinically characterized by memory loss and impaired cognitive function. Cholinergic enzyme deficiency and oxidative stress are the two major factors implicated in the pathogenesis of AD. The symptomatic treatment, as of now, is the use of cholinesterase inhibitors toward cholinergic "downturn." Therefore, there is a search for compounds that will be useful in focused therapies. There has been suggestion that Terminalia chebula fruit would be a potential source...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29142315/hiv-1-counteracts-an-innate-restriction-by-amyloid-precursor-protein-resulting-in-neurodegeneration
#11
Qingqing Chai, Vladimir Jovasevic, Viacheslav Malikov, Yosef Sabo, Scott Morham, Derek Walsh, Mojgan H Naghavi
While beta-amyloid (Aβ), a classic hallmark of Alzheimer's disease (AD) and dementia, has long been known to be elevated in the human immunodeficiency virus type 1 (HIV-1)-infected brain, why and how Aβ is produced, along with its contribution to HIV-associated neurocognitive disorder (HAND) remains ill-defined. Here, we reveal that the membrane-associated amyloid precursor protein (APP) is highly expressed in macrophages and microglia, and acts as an innate restriction against HIV-1. APP binds the HIV-1 Gag polyprotein, retains it in lipid rafts and blocks HIV-1 virion production and spread...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29142143/dha-supplementation-improves-cognitive-function-via-enhancing-a%C3%AE-mediated-autophagy-in-chinese-elderly-with-mild-cognitive-impairment-a-randomised-placebo-controlled-trial
#12
Yan-Ping Zhang, Yinyin Lou, Jing Hu, Rujuan Miao, Fei Ma
BACKGROUND: Higher docosahexaenoic acid (DHA) intake is inversely correlated with relative risk of Alzheimer's disease. The potential benefits of DHA supplementation in people with mild cognitive impairment (MCI) have not been fully examined. OBJECTIVE: Our study aimed to assess the effect of a 24-month DHA supplementation on cognitive function and amyloid beta (Aβ)-mediated autophagy in elderly subjects with MCI. METHODS: This was a randomised, double-blind, placebo-controlled trial in Tianjin, China...
November 15, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29142073/gga1-regulates-signal-dependent-sorting-of-bace1-to-recycling-endosomes-which-moderates-a%C3%AE-production
#13
Wei Hong Toh, Pei Zhi Cheryl Chia, Mohammed Iqbal Hossain, Paul A Gleeson
The diversion of the membrane-bound β-secretase BACE1 from the endo-lysosomal pathway to recycling endosomes represents an important transport step in the regulation of amyloid beta (Aβ) production. However, the mechanisms that regulate endosome sorting of BACE1 are poorly understood. Here we assessed the transport of BACE1 from early to recycling endosomes and have identified essential roles for the SNX4-mediated, signal independent pathway and for a novel signal-mediated pathway. The signal-mediated pathway is regulated by the phosphorylation of the acidic cluster-dileucine DISLL cytoplasmic tail motif of BACE1...
November 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29141588/parkinson-disease-polygenic-risk-score-is-associated-with-parkinson-disease-status-and-age-at-onset-but-not-with-alpha-synuclein-cerebrospinal-fluid-levels
#14
Laura Ibanez, Umber Dube, Benjamin Saef, John Budde, Kathleen Black, Alexandra Medvedeva, Jorge L Del-Aguila, Albert A Davis, Joel S Perlmutter, Oscar Harari, Bruno A Benitez, Carlos Cruchaga
BACKGROUND: The genetic architecture of Parkinson's Disease (PD) is complex and not completely understood. Multiple genetic studies to date have identified multiple causal genes and risk loci. Nevertheless, most of the expected genetic heritability remains unexplained. Polygenic risk scores (PRS) may provide greater statistical power and inform about the genetic architecture of multiple phenotypes. The aim of this study was to test the association between PRS and PD risk, age at onset and cerebrospinal fluid (CSF) biomarkers (α-synuclein, Aβ1-42, t-tau and p-tau)...
November 15, 2017: BMC Neurology
https://www.readbyqxmd.com/read/29138762/identifying-cu-ii-amyloid-peptide-binding-intermediates-in-the-early-stages-of-aggregation-by-resonance-raman-spectroscopy-a-simulation-study
#15
Hao Ren, Yu Zhang, Sibei Guo, Na Lin, Li Deng, Tongtao Yue, Fang Huang
The aggregation of amyloid beta (Aβ) peptides plays a crucial role in the pathology and etiology of Alzheimer's disease. Experimental evidence shows that copper ion is an aggregation-prone species with the ability to coordinately bind to Aβ and further induce the formation of neurotoxic Aβ oligomers. However, the detailed structures of Cu(ii)-Aβ complexes have not been illustrated, and the kinetics and dynamics of the Cu(ii) binding are not well understood. Two Cu(ii)-Aβ complexes have been proposed to exist under physiological conditions, and another two might exist at higher pH values...
November 15, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29137322/the-c-jun-n-terminal-kinase-plays-a-key-role-in-ocular-degenerative-changes-in-a-mouse-model-of-alzheimer-disease-suggesting-a-correlation-between-ocular-and-brain-pathologies
#16
Lucia Buccarello, Alessandra Sclip, Matteo Sacchi, Anna Maria Castaldo, Ilaria Bertani, Andrea ReCecconi, Silvia Maestroni, Gianpaolo Zerbini, Paolo Nucci, Tiziana Borsello
Recently a range of ocular manifestations such as retinal and lens amyloid-beta accumulation and retinal nerve fiber layer loss have been proposed as potential biomarkers in Alzheimer disease (AD). The TgCRND8 mouse model of AD exhibits age-dependent amyloid β (Aβ) oligomers accumulation and cognitive defects, amyloid plaques and hyperphosphorylated Tau deposition and inflammation. We proved the correlation between ocular pathologies and AD, observing increased levels of p-APP and p-Tau, accumulation of Aβ oligomers in the retina, eye, and optic nerve...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135331/imaging-microglial-activation-and-amyloid-burden-in-amnestic-mild-cognitive-impairment
#17
Dunja Knezevic, Nicolaas Paul Lg Verhoeff, Sina Hafizi, Antonio P Strafella, Ariel Graff-Guerrero, Tarek Rajji, Bruce G Pollock, Sylvain Houle, Pablo M Rusjan, Romina Mizrahi
Amnestic mild cognitive impairment (aMCI) is defined as a transitional state between normal aging and Alzheimer's disease (AD). Given the replicated finding of increased microglial activation in AD, we sought to investigate whether microglial activation is also elevated in aMCI and whether it is related to amyloid beta (Aβ) burden in-vivo . Eleven aMCI participants and 14 healthy volunteers completed positron emission tomography (PET) scans with [(18)F]-FEPPA and [(11)C]-PIB. Given the known sensitivity in affinity of second-generation TSPO radioligands, participants were genotyped for the TSPO polymorphism and only high-affinity binders were included...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29134927/cerebral-amyloid-angiopathy-associated-with-inflammation-a-systematic-review-of-clinical-and-imaging-features-and-outcome
#18
Andrej Corovic, Siobhan Kelly, Hugh S Markus
Background Cerebral amyloid angiopathy associated with inflammation is an increasingly recognized condition, characterized by an inflammatory response to the vascular deposits of β-amyloid within the brain that are the hallmark of cerebral amyloid angiopathy. Two main patterns of this inflammatory response have been identified to date: one involving a perivascular inflammatory cell infiltrate (cerebral amyloid angiopathy-related inflammation); the other a transmural vasculitic process (A-beta related angiitis)...
January 1, 2017: International Journal of Stroke: Official Journal of the International Stroke Society
https://www.readbyqxmd.com/read/29134465/current-role-for-biomarkers-in-clinical-diagnosis-of-alzheimer-disease-and-frontotemporal-dementia
#19
REVIEW
Nasim Sheikh-Bahaei, Seyed Ahmad Sajjadi, Aimee L Pierce
Purpose of review Alzheimer's disease (AD) and frontotemporal dementia can often be diagnosed accurately with careful clinical history, cognitive testing, neurological examination, and structural brain MRI. However, there are certain circumstances wherein detection of specific biomarkers of neurodegeneration or underlying AD pathology will impact the clinical diagnosis or treatment plan. We will review the currently available biomarkers for AD and frontotemporal dementia (FTD) and discuss their clinical importance...
November 14, 2017: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/29132916/insulin-degrading-enzyme-in-the-fight-against-alzheimer-s-disease
#20
REVIEW
Igor V Kurochkin, Enrico Guarnera, Igor N Berezovsky
After decades of research and clinical trials there is still no cure for Alzheimer's disease (AD). While impaired clearance of amyloid beta (Aβ) peptides is considered as one of the major causes of AD, it was recently complemented by a potential role of other toxic amyloidogenic species. Insulin-degrading enzyme (IDE) is the proteolytic culprit of various β-forming peptides, both extracellular and intracellular. On the basis of demonstrated allosteric activation of IDE against Aβ, it is possible to propose a new strategy for the targeted IDE-based cleansing of different toxic aggregation-prone peptides...
November 10, 2017: Trends in Pharmacological Sciences
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