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https://www.readbyqxmd.com/read/29161341/distinct-spatiotemporal-accumulation-of-n-truncated-and-full-length-amyloid-%C3%AE-42-in-alzheimer-s-disease
#1
Mitsuru Shinohara, Shunsuke Koga, Takuya Konno, Jeremy Nix, Motoko Shinohara, Naoya Aoki, Pritam Das, Joseph E Parisi, Ronald C Petersen, Terrone L Rosenberry, Dennis W Dickson, Guojun Bu
Accumulation of amyloid-β peptides is a dominant feature in the pathogenesis of Alzheimer's disease; however, it is not clear how individual amyloid-β species accumulate and affect other neuropathological and clinical features in the disease. Thus, we compared the accumulation of N-terminally truncated amyloid-β and full-length amyloid-β, depending on disease stage as well as brain area, and determined how these amyloid-β species respectively correlate with clinicopathological features of Alzheimer's disease...
November 17, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29155576/chronic-arsenic-exposure-increases-a%C3%AE-1-42-production-and-rage-expression-in-rat-brain
#2
Sandra Aurora Niño, Guadalupe Martel-Gallegos, Adriana Castro-Zavala, Benita Ortega-Berlanga, Juan Manuel Delgado, Hector Hernandez-Mendoza, E Romero-Guzman, Judith Rios-Lugo, Sergio Rosales-Mendoza, María Esther Jiménez-Capdeville, Sergio Zarazua
Chronic arsenic exposure during development is associated with alterations of chemical transmission and demyelination, which result in cognitive deficits and peripheral neuropathies. At cellular level, arsenic toxicity involves increased generation of reactive species that induce severe cellular alterations such as DNA fragmentation, apoptosis and lipid peroxidation. It has been proposed that arsenic-associated neurodegeneration could evolve to Alzheimer disease in later life.1,2 In this study, the effects of chronic exposure to inorganic arsenic (3 ppm by drinking water) in Wistar rats on the production and elimination of Amyloid-β (Aβ) were evaluated...
November 20, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29150274/neuroprotective-potential-of-high-dose-biotin
#3
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/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
#4
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/29142073/gga1-regulates-signal-dependent-sorting-of-bace1-to-recycling-endosomes-which-moderates-a%C3%AE-production
#5
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/29141208/crispr-transcriptional-activation-analysis-unmasks-an-occult-%C3%AE-secretase-processivity-defect-in-familial-alzheimer-s-disease-skin-fibroblasts
#6
Keiichi Inoue, Luis M A Oliveira, Asa Abeliovich
Mutations in presenilin (PSEN) 1 and 2, which encode components of the γ-secretase (GS) complex, cause familial Alzheimer's disease (FAD). It is hypothesized that altered GS-mediated processing of the amyloid precursor protein (APP) to the Aβ42 fragment, which is accumulated in diseased brain, may be pathogenic. Here, we describe an in vitro model system that enables the facile analysis of neuronal disease mechanisms in non-neuronal patient cells using CRISPR gene activation of endogenous disease-relevant genes...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29114105/neuregulin-3-signaling-mediates-nicotine-dependent-synaptic-plasticity-in-the-orbitofrontal-cortex-and-cognition
#7
Luyi Zhou, Miranda L Fisher, Robert D Cole, Thomas J Gould, Vinay Parikh, Pavel I Ortinski, Jill R Turner
Neuregulin 3 (NRG3) and ErbB4 have been linked to nicotine addiction; however, the neuronal mechanisms and behavioral consequences of NRG3-ErbB4 sensitivity to nicotine remain elusive. Recent literature suggests that relapse to smoking is due to a lack of impulsive control, which is thought to be due to altered functioning within the orbitofrontal cortex (OFC). Therefore, we examined circuitry changes within this structure following nicotine application. We report that nicotine controls synaptic plasticity in the OFC through NRG3/ErbB4-dependent regulation of GABAergic inhibition...
November 7, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29111366/corrigendum-to-design-and-synthesis-of-bicyclic-acetals-as-beta-secretase-bace1-inhibitors-bioorg-med-chem-25-2017-5077-5083
#8
Riccardo Innocenti, Elena Lenci, Gloria Menchi, Alberto Pupi, Andrea Trabocchi
No abstract text is available yet for this article.
October 27, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29107423/multifunctional-iminochromene-2h-carboxamide-derivatives-containing-different-aminomethylene-triazole-with-bace1-inhibitory-neuroprotective-and-metal-chelating-properties-targeting-alzheimer-s-disease
#9
Aida Iraji, Omidreza Firuzi, Mehdi Khoshneviszadeh, Marjan Tavakkoli, Mohammad Mahdavi, Hamid Nadri, Najmeh Edraki, Ramin Miri
Alzheimer's disease (AD) is a neurodegenerative disorder known for the presence of amyloid beta plaques resulting from the sequential action of β-secretase and γ-secretase on amyloid precursor protein. We developed and synthesized, through click reactions, a new family of iminochromene carboxamides containing different aminomethylene triazole. The BACE1 inhibition, neuroprotective capacity and metal chelation of these derivatives make them ideal candidates against AD. Most of the synthesized compounds were shown to have potent BACE1 inhibitory activity in a FRET assay, with an IC50 value of 2...
December 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29080748/overexpression-of-snx7-reduces-a%C3%AE-production-by-enhancing-lysosomal-degradation-of-app
#10
Shaohua Xu, Lu Zhang, Lennart Brodin
Abnormal production of amyloid-β peptides (Aβ) by proteolytic processing of amyloid precursor protein (APP) is thought to be central to the pathogenesis of Alzheimer's disease (AD). Although many efforts have been made to investigate mechanisms that regulate APP processing, many details remain incompletely understood. Sorting nexins (SNXs) are a family of proteins which are involved in many intracellular trafficking events. Several SNXs have been implicated in APP processing and Aβ production. In this study, we extended the investigation to SNX7...
October 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29078331/lack-of-bace1-s-palmitoylation-reduces-amyloid-burden-and-mitigates-memory-deficits-in-transgenic-mouse-models-of-alzheimer-s-disease
#11
Robert J Andrew, Celia G Fernandez, Molly Stanley, Hong Jiang, Phuong Nguyen, Richard C Rice, Virginie Buggia-Prévot, Pierre De Rossi, Kulandaivelu S Vetrivel, Raza Lamb, Arnau Argemi, Emilie S Allaert, Elle M Rathbun, Sofia V Krause, Steven L Wagner, Angèle T Parent, David M Holtzman, Gopal Thinakaran
Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by pathological brain lesions and a decline in cognitive function. β-Amyloid peptides (Aβ), derived from proteolytic processing of amyloid precursor protein (APP), play a central role in AD pathogenesis. β-Site APP cleaving enzyme 1 (BACE1), the transmembrane aspartyl protease which initiates Aβ production, is axonally transported in neurons and accumulates in dystrophic neurites near cerebral amyloid deposits in AD. BACE1 is modified by S-palmitoylation at four juxtamembrane cysteine residues...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29072895/low-frequency-pulsed-electromagnetic-field-is-able-to-modulate-mirnas-in-an-experimental-cell-model-of-alzheimer-s-disease
#12
Enrica Capelli, Filippo Torrisi, Letizia Venturini, Maria Granato, Lorenzo Fassina, Giuseppe Francesco Damiano Lupo, Giovanni Ricevuti
The aim of the present study was to investigate on the effects of a low-frequency pulsed electromagnetic field (LF-PEMF) in an experimental cell model of Alzheimer's disease (AD) to assess new therapies that counteract neurodegeneration. In recent scientific literature, it is documented that the deep brain stimulation via electromagnetic fields (EMFs) modulates the neurophysiological activity of the pathological circuits and produces clinical benefits in AD patients. EMFs are applied for tissue regeneration because of their ability to stimulate cell proliferation and immune functions via the HSP70 protein family...
2017: Journal of Healthcare Engineering
https://www.readbyqxmd.com/read/29065581/low-frequency-pulsed-electromagnetic-field-is-able-to-modulate-mirnas-in-an-experimental-cell-model-of-alzheimer-s-disease
#13
Enrica Capelli, Filippo Torrisi, Letizia Venturini, Maria Granato, Lorenzo Fassina, Giuseppe Francesco Damiano Lupo, Giovanni Ricevuti
The aim of the present study was to investigate on the effects of a low-frequency pulsed electromagnetic field (LF-PEMF) in an experimental cell model of Alzheimer's disease (AD) to assess new therapies that counteract neurodegeneration. In recent scientific literature, it is documented that the deep brain stimulation via electromagnetic fields (EMFs) modulates the neurophysiological activity of the pathological circuits and produces clinical benefits in AD patients. EMFs are applied for tissue regeneration because of their ability to stimulate cell proliferation and immune functions via the HSP70 protein family...
2017: Journal of Healthcare Engineering
https://www.readbyqxmd.com/read/29052456/population-density-analysis-for-determining-the-protonation-state-of-the-catalytic-dyad-in-bace1-tertiary-carbinamine-based-inhibitor-complex
#14
Carlos Gueto-Tettay, Luis Pelaez-Bedoya, Juan Carlos Drosos-Ramirez
BACE1 is an aspartyl protease with a very relevant role in medicinal chemistry related to Alzheimer Disease since it has demonstrated to be a promising therapeutic target for inhibition and possible control for the progress of the peptide accumulation characteristic of this pathology. The enzymatic activity of this protein is given by the aspartic dyad, Asp93 and Asp289, which can adopt several protonation states depending on the chemical nature of its inhibitors, this is, monoprotonated, diprotonated and di-deprotonated states...
October 20, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29040655/effects-of-1950-mhz-radiofrequency-electromagnetic-fields-on-a%C3%AE-processing-in-human-neuroblastoma-and-mouse-hippocampal-neuronal-cells
#15
Jeongyeon Park, Jong Hwa Kwon, Nam Kim, Kiwon Song
Alzheimer's disease (AD) is a neurodegenerative disease leading to progressive loss of memory and other cognitive functions. One of the well-known pathological markers of AD is the accumulation of amyloid-beta protein (Aβ), and its plaques, in the brain. Recent studies using Tg-5XFAD mice as a model of AD have reported that exposure to radiofrequency electromagnetic fields (RF-EMF) from cellular phones reduced Aβ plaques in the brain and showed beneficial effects on AD. In this study, we examined whether exposure to 1950 MHz RF-EMF affects Aβ processing in neural cells...
October 6, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/29038004/flavonoid-rich-ethanol-extract-from-the-leaves-of-diospyros-kaki-attenuates-cognitive-deficits-amyloid-beta-production-oxidative-stress-and-neuroinflammation-in-app-ps1-transgenic-mice
#16
Yingjuan Ma, Bin Ma, Yuying Shang, Qingqing Yin, Yan Hong, Song Xu, Chao Shen, Xunyao Hou, Xueping Liu
Amyloid-β peptide (Aβ) initiates a cascade of pathological events, including activation of microglial cells, oxidative stress, and inflammation, leading to neuronal death and the typical pathological changes in Alzheimer's disease (AD). Flavonoids have been reported to exert neuroprotective activities, not only through their generally accepted antioxidant effects, but also through their ability to protect against neurotoxin-induced injury. Flavonoids reduce Aβ production, inhibit neuroinflammation, increase cerebrovascular function, and improve cognitive performance...
October 13, 2017: Brain Research
https://www.readbyqxmd.com/read/29033830/the-decrease-of-uch-l1-activity-is-a-common-mechanism-responsible-for-a%C3%AE-42-accumulation-in-alzheimer-s-and-vascular-disease
#17
Michela Guglielmotto, Debora Monteleone, Valeria Vasciaveo, Ivan Enrico Repetto, Giusi Manassero, Massimo Tabaton, Elena Tamagno
Alzheimer's disease (AD) is a multifactorial pathology causing common brain spectrum disorders in affected patients. These mixed neurological disorders not only include structural AD brain changes but also cerebrovascular lesions. The main aim of the present issue is to find the factors shared by the two pathologies. The decrease of ubiquitin C-terminal hydrolase L1 (Uch-L1), a major neuronal enzyme involved in the elimination of misfolded proteins, was observed in ischemic injury as well as in AD, but its role in the pathogenesis of AD is far to be clear...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29027981/bace1-function-and-inhibition-implications-of-intervention-in-the-amyloid-pathway-of-alzheimer-s-disease-pathology
#18
REVIEW
Gerald Koelsch
Alzheimer's disease (AD) is a fatal progressive neurodegenerative disorder characterized by increasing loss in memory, cognition, and function of daily living. Among the many pathologic events observed in the progression of AD, changes in amyloid β peptide (Aβ) metabolism proceed fastest, and precede clinical symptoms. BACE1 (β-secretase 1) catalyzes the initial cleavage of the amyloid precursor protein to generate Aβ. Therefore inhibition of BACE1 activity could block one of the earliest pathologic events in AD...
October 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28994117/melatonin-ameliorates-a%C3%AE-1-42-induced-alzheimer-s-cognitive-deficits-in-mouse-model
#19
Yu-Hang Gong, Nan Hua, Xuan Zang, Tao Huang, Ling He
OBJECTIVES: The objective of this study was to evaluate whether melatonin could ameliorate cognitive function in Aβ1-42 -induced mouse model and its underlying mechanisms. METHODS: Series behaviour tests were performed to demonstrate the amelioration of cognitive function of the Alzheimer's disease (AD) mice induced by Aβ1-42 . Additionally, enzyme-linked immunosorbent assay was applied to detect the expression of Aβ1-42 , BACE1 and p-tau protein in the brain of the AD mice...
October 10, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28993723/bace1-dependent-neuregulin-1-signaling-an-implication-for-schizophrenia
#20
REVIEW
Zhengrong Zhang, Jing Huang, Yong Shen, Rena Li
Schizophrenia is a chronic psychiatric disorder with a lifetime prevalence of about 1% in the general population. Recent studies have shown that Neuregulin-1 (Nrg1) is a candidate gene for schizophrenia. At least 15 alternative splicing of NRG1 isoforms all contain an extracellular epidermal growth factor (EGF)-like domain, which is sufficient for Nrg1 biological activity including the formation of myelin sheaths and the regulation of synaptic plasticity. It is known that Nrg1 can be cleaved by β-secretase (BACE1) and the resulting N-terminal fragment (Nrg1-ntf) binds to receptor tyrosine kinase ErbB4, which activates Nrg1/ErbB4 signaling...
2017: Frontiers in Molecular Neuroscience
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