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https://www.readbyqxmd.com/read/28437839/semicarbazide-sensitive-amine-oxidase-vascular-adhesion-protein-1-inhibition-reduces-lipopolysaccharide-induced-neuroinflammation
#1
Serena Becchi, Alberto Buson, Jonathan Foot, Wolfgang Jarolimek, Bernard W Balleine
BACKGROUND AND PURPOSE: Neuroinflammation is initiated by a variety of stimuli including infections, sepsis, neurodegenerative diseases or traumatic brain injury and if not adequately controlled can lead to various degrees of neuronal damage and behavioural impairment. A critical event in the initial steps of inflammation is neutrophil extravasation. Semicarbazide sensitive amine oxidase (SSAO, also known as vascular adhesion protein 1 or VAP-1) regulates neutrophil adhesion and extravasation...
April 24, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28437540/characterization-of-gene-expression-phenotype-in-amyotrophic-lateral-sclerosis-monocytes
#2
Weihua Zhao, David R Beers, Kristopher G Hooten, Douglas H Sieglaff, Aijun Zhang, Shanker Kalyana-Sundaram, Christopher M Traini, Wendy S Halsey, Ashley M Hughes, Ganesh M Sathe, George P Livi, Guo-Huang Fan, Stanley H Appel
Importance: Amyotrophic lateral sclerosis (ALS) is a common adult-onset neurodegenerative disease characterized by selective loss of upper and lower motor neurons. Patients with ALS have persistent peripheral and central inflammatory responses including abnormally functioning T cells and activated microglia. However, much less is known about the inflammatory gene profile of circulating innate immune monocytes in these patients. Objective: To characterize the transcriptomics of peripheral monocytes in patients with ALS...
April 24, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28437250/ionizing-radiation-reduces-adam10-expression-in-brain-microvascular-endothelial-cells-undergoing-stress-induced-senescence
#3
Lucinda S McRobb, Matthew J McKay, Jennifer R Gamble, Michael Grace, Vaughan Moutrie, Estevam D Santos, Vivienne S Lee, Zhenjun Zhao, Mark P Molloy, Marcus A Stoodley
Cellular senescence is associated with aging and is considered a potential contributor to age-associated neurodegenerative disease. Exposure to ionizing radiation increases the risk of developing premature neurovascular degeneration and dementia but also induces premature senescence. As cells of the cerebrovascular endothelium are particularly susceptible to radiation and play an important role in brain homeostasis, we investigated radiation-induced senescence in brain microvascular endothelial cells (EC). Using biotinylation to label surface proteins, streptavidin enrichment and proteomic analysis, we analyzed the surface proteome of stress-induced senescent EC in culture...
April 17, 2017: Aging
https://www.readbyqxmd.com/read/28437187/synergy-between-choroid-plexus-epithelial-cells-conditioned-medium-and-knockout-serum-replacement-converts-human-adipose-derived-stem-cells-to-dopamine-secreting-neurons
#4
Mahdi Eskandarian Boroujeni, Mossa Gardaneh, Mehrnoosh Hasan Shahriari, Abbas Aliaghaei, Sanaz Hasani
Human adipose-derived stem cells (hADSCs) have great capacity to differentiate into mesodermal origins as well as non-mesodermal lineages including neural cells. This valuable feature paves the way for the therapeutic application of hADSCs for neurodegenerative maladies such as Parkinson's disease (PD). We tested the capacity of Choroid Plexus epithelial cells-conditioned medium (CPEC-CM) alone or cocktailed with knock-out serum (KS) to induce dopaminergic differentiation of hADSCs. To this end, hADSCs from lipoaspirate were phenotypically characterized and shown to maintain mesodermal multipotency so selected media easily differentiated them into osteoblasts, chondrocytes and adipocytes...
March 2, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28437088/hilaq-a-novel-strategy-for-newly-synthesized-protein-quantification
#5
Yuanhui Ma, Daniel B McClatchy, Salim Barkallah, William W Wood, John R Yates Iii
Here we describe a new strategy, HILAQ (Heavy Isotope Labeled Azidohomoalanine Quantification), to rapidly quantify the molecular vulnerability profile to oxytosis, which is an oxidative stress-induced programed cell death pathway that has been reported to be involved in aging and neurodegenerative diseases. HILAQ was able to quantify 1,962 Newly Synthesized Proteins (NSPs) after 1h pulse labeling in HEK293T cell line, while 353 proteins were quantified using the previously published QuaNCAT protocol. HILAQ was successfully applied to the HT22 oxytosis model...
April 24, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28436392/the-dna-damage-response-in-neurons-die-by-apoptosis-or-survive-in-a-senescence-like-state
#6
Edward Fielder, Thomas von Zglinicki, Diana Jurk
Neurons are exposed to high levels of DNA damage from both physiological and pathological sources. Neurons are post-mitotic and their loss cannot be easily recovered from; to cope with DNA damage a complex pathway called the DNA damage response (DDR) has evolved. This recognizes the damage, and through kinases such as ataxia-telangiectasia mutated (ATM) recruits and activates downstream factors that mediate either apoptosis or survival. This choice between these opposing outcomes integrates many inputs primarily through a number of key cross-road proteins, including ATM, p53, and p21...
April 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28436304/the-pten-inhibitor-bpv-pic-promotes-neuroprotection-against-amyloid-%C3%AE-peptide-25-35-induced-oxidative-stress-and-neurotoxicity
#7
Xiao-Ying Liu, Li-Jing Zhang, Zhou Chen, Li-Bin Liu
OBJECTIVES: The aim of this study was to elucidate the mechanism underlying the neuroprotective effects of the phosphatase and tensin homolog (PTEN) inhibitor, bisperoxovanadium-pic [bpV(pic)]. METHODS: We determined the effects of bpV(pic) on amyloid-β-peptide-(25-35)-induced neurotoxicity, particularly intracellular reactive oxygen species (ROS) production and mitochondria-mediated apoptotic signaling, in a human neuroblastoma (SH-SY5Y) cell model. RESULTS: We found that exposure of SH-SY5Y cells to amyloid β peptides (Aβ25-35) resulted in a significant reduction in cell viability accompanied by increased lactate dehydrogenase (LDH) release, elevated levels of intracellular ROS, and decreased superoxide dismutase (SOD) activities, all of which were reversed by co-treatment with bpV(pic)...
April 23, 2017: Neurological Research
https://www.readbyqxmd.com/read/28436203/endoplasmic-reticulum-proteostasis-impairment-in-aging
#8
REVIEW
Gabriela Martínez, Claudia Duran-Aniotz, Felipe Cabral-Miranda, Juan P Vivar, Claudio Hetz
Perturbed neuronal proteostasis is a salient feature shared by both aging and protein misfolding disorders. The proteostasis network controls the health of the proteome by integrating pathways involved in protein synthesis, folding, trafficking, secretion, and their degradation. A reduction in the buffering capacity of the proteostasis network during aging may increase the risk to undergo neurodegeneration by enhancing the accumulation of misfolded proteins. As almost one-third of the proteome is synthetized at the endoplasmic reticulum (ER), maintenance of its proper function is fundamental to sustain neuronal function...
April 23, 2017: Aging Cell
https://www.readbyqxmd.com/read/28435985/elucidating-the-a%C3%AE-42-anti-aggregation-mechanism-of-action-of-tramiprosate-in-alzheimer-s-disease-integrating-molecular-analytical-methods-pharmacokinetic-and-clinical-data
#9
Petr Kocis, Martin Tolar, Jeremy Yu, William Sinko, Soumya Ray, Kaj Blennow, Howard Fillit, John A Hey
BACKGROUND: Amyloid beta (Aβ) oligomers play a critical role in the pathogenesis of Alzheimer's disease (AD) and represent a promising target for drug development. Tramiprosate is a small-molecule Aβ anti-aggregation agent that was evaluated in phase III clinical trials for AD but did not meet the primary efficacy endpoints; however, a pre-specified subgroup analysis revealed robust, sustained, and clinically meaningful cognitive and functional effects in patients with AD homozygous for the ε4 allele of apolipoprotein E4 (APOE4/4 homozygotes), who carry an increased risk for the disease...
April 24, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28435972/-glp-1-gip-gcg-receptor-triagonist-improves-the-cognitive-behaviors-in-triple-transgenic-mice-of-alzheimer-s-disease
#10
Juan-Juan Jiao, Christian Hölscher, Tian Li, Xue-Fan Dong, Xue-Song Qu, Yue Cao, Mei-Na Wu, Zhao-Jun Wang, Jin-Shun Qi
Alzheimer's disease (AD) is a progressively neurodegenerative disorder, which seriously affects human health but is still irreversible up to now. Recent studies indicate that type 2 diabetes mellitus (T2DM) is an important risk factor for AD, and the drugs used for treatment of T2DM have shown some neuroprotective effects in the treatment of AD. Glucagon-like peptide-1 (GLP-1)/ glucose-dependent insulinotropic polypeptide (GIP)/glucagon (Gcg) receptor Triagonist is a new monomeric polypeptide equally activating the GLP-1/GIP/Gcg receptors, which is built on the basis of GLP-1/Gcg receptor coagonist core sequence, and incorporated with partial amino acids of GIP...
April 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28435839/the-frequency-of-yeast-psi-prion-formation-is-increased-during-chronological-ageing
#11
Shaun H Speldewinde, Chris M Grant
Ageing involves a time-dependent decline in a variety of intracellular mechanisms and is associated with cellular senescence. This can be exacerbated by prion diseases which can occur in a sporadic manner, predominantly during the later stages of life. Prions are infectious, self-templating proteins responsible for several neurodegenerative diseases in mammals and several prion-forming proteins have been found in yeast. We show here that the frequency of formation of the yeast [PSI(+) ] prion, which is the altered form of the Sup35 translation termination factor, is increased during chronological ageing...
March 27, 2017: Microbial Cell
https://www.readbyqxmd.com/read/28435465/hypertension-cerebrovascular-impairment-and-cognitive-decline-in-aged-a%C3%AE-pp-ps1-mice
#12
Maximilian Wiesmann, Valerio Zerbi, Diane Jansen, Dieter Lütjohann, Andor Veltien, Arend Heerschap, Amanda J Kiliaan
Cardiovascular risk factors, especially hypertension, are also major risk factors for Alzheimer's disease (AD). To elucidate the underlying vascular origin of neurodegenerative processes in AD, we investigated the relation between systolic blood pressure (SBP) cerebral blood flow (CBF) and vasoreactivity with brain structure and function in a 16-18 months old double transgenic AβPPswe/PS1dE9 (AβPP/PS1) mouse model for AD. These aging AβPP/PS1 mice showed an increased SBP linked to a declined regional CBF...
2017: Theranostics
https://www.readbyqxmd.com/read/28435163/progranulin-lysosomal-regulation-and-neurodegenerative-disease
#13
REVIEW
Aimee W Kao, Andrew McKay, Param Priya Singh, Anne Brunet, Eric J Huang
The discovery that heterozygous and homozygous mutations in the gene encoding progranulin are causally linked to frontotemporal dementia and lysosomal storage disease, respectively, reveals previously unrecognized roles of the progranulin protein in regulating lysosome biogenesis and function. Given the importance of lysosomes in cellular homeostasis, it is not surprising that progranulin deficiency has pleiotropic effects on neural circuit development and maintenance, stress response, innate immunity and ageing...
April 24, 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/28435076/design-synthesis-biological-evaluation-and-molecular-modelling-of-2-2-aryloxyphenyl-1-4-dihydroisoquinolin-3-2h-ones-a-novel-class-of-tspo-ligands-modulating-amyloid-%C3%AE-induced-mptp-opening
#14
Ahmed Elkamhawy, Jung-Eun Park, Ahmed H E Hassan, Ae Nim Pae, Jiyoun Lee, Beoung-Geon Park, Sora Paik, Jimin Do, Jong-Hyun Park, Ki Duk Park, Bongjin Moon, Woo Kyu Park, Heeyeong Cho, Dae Young Jeong, Eun Joo Roh
Translocator protein (TSPO) is involved in modulating mitochondrial permeability transition pore (mPTP) opening/closure leading to either apoptotic cell death via opening of mPTP or cell protection mediated by mPTP blocking and hence intercepting mPTP induced apoptosis. Herein, 2-(2-aryloxyphenyl)-1,4-dihydroisoquinolin-3(2H)-one derivatives have been designed and synthesized as new modulators for amyloid-β-induced mPTP opening. Among all, compound 7c remarkably enhanced mPTP opening while compound 7e showed the highest mPTP blocking activity...
April 20, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28435052/neurovascular-neuroenergetic-coupling-axis-in-the-brain-master-regulation-by-nitric-oxide-and-consequences-in-aging-and-neurodegeneration
#15
REVIEW
Cátia F Lourenço, Ana Ledo, Rui M Barbosa, João Laranjinha
The strict energetic demands of the brain require that nutrient supply and usage be fine-tuned in accordance with the specific temporal and spatial patterns of ever-changing levels of neuronal activity. This is achieved by adjusting local cerebral blood flow (CBF) as a function of activity level - neurovascular coupling - and by changing how energy substrates are metabolized and shuttled amongst astrocytes and neurons - neuroenergetic coupling. Both activity-dependent increase of CBF and O2 and glucose utilization by active neural cells are inextricably linked, establishing a functional metabolic axis in the brain, the neurovascular-neuroenergetic coupling axis...
April 20, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28435046/a-multilevel-roi-features-based-machine-learning-method-for-detection-of-morphometric-biomarkers-in-parkinson-s-disease
#16
Bo Peng, Suhong Wang, Zhiyong Zhou, Yan Liu, Baotong Tong, Tao Zhang, Yakang Dai
Machine learning methods have been widely used in recent years for detection of neuroimaging biomarkers in regions of interest (ROIs) and assisted diagnosis of neurodegenerative diseases. The innovation of this study is to use multilevel-ROI-features-based machine learning method to detect sensitive morphometric biomarkers in Parkinson's disease (PD). Specifically, the low-level ROI features (gray matter volume, cortical thickness, etc.) and high-level correlative features (connectivity between ROIs) are integrated to make the multilevel ROI features...
April 20, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28434855/health-care-use-before-a-first-demyelinating-event-suggestive-of-a-multiple-sclerosis-prodrome-a-matched-cohort-study
#17
José M A Wijnands, Elaine Kingwell, Feng Zhu, Yinshan Zhao, Tanja Högg, Karen Stadnyk, Okechukwu Ekuma, Xinya Lu, Charity Evans, John D Fisk, Ruth Ann Marrie, Helen Tremlett
BACKGROUND: Degenerative processes in neurodegenerative diseases can start years before clinical manifestation. We aimed to establish whether a multiple sclerosis prodromal period exists by examining patterns of health-care use before a first demyelinating event. METHODS: In this matched cohort study, we used data from linked health administrative and clinical databases from four Canadian provinces (British Columbia, Saskatchewan, Manitoba, and Nova Scotia) to compare hospital, physician, and prescription use data from people with multiple sclerosis and matched general population controls in the 5 years before the first demyelinating disease claim (health administrative index date) or clinically reported symptom onset (clinical index date)...
April 20, 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28434268/ubiquitin-c-terminal-hydrolase-l1-uch-l1-as-a-therapeutic-and-diagnostic-target-in-neurodegeneration-neurotrauma-and-neuro-injuries
#18
Kevin K Wang, Zhihui Yang, George Sarkis, Isabel Torres, Vijaya Raghavan
Since its discovery as a major CNS-abundant protein 25 years ago, Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has emerged as an important enzyme in regulating brain protein metabolism, by coupling to the proteasome pathway of protein degradation. Areas covered: UCH-L1 is implicated in both familial and sporadic Parkinson disease and other chronic neurodegenerative diseases. Also, UCH-L1 has been recently emerging as a biofluid-based biomarker for various forms of acute neurotrauma and CNS injury. Expert opinion: The loss of UCH-L1 activity coupled with the gain of proteinopathy function are linked to neurodegeneration such as Parkinsonism and Alzheimer's disease...
April 24, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28434243/-clinical-and-neuropathological-characteristics-of-dementia-with-lewy-bodies
#19
János Bencze, Viktória Simon, Erika Bereczki, Réka Majer, Gréta Varkoly, Balázs Murnyák, János Kálmán, Tibor Hortobágyi
Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia. The accurate diagnosis is often possible only by neuropathological examination. The morphologic hallmarks are the presence of α-synuclein-rich Lewy bodies and Lewy neurites, identical to those seen in Parkinson's disease (PD) and Parkinson's disease dementia (PDD). Neurotransmitter deficits, synaptic and ubiquitin-proteasome system (UPS) dysfunction play major role in the pathomechanism. Characteristic symptoms are cognitive fluctuation, parkinsonism and visual hallucinations...
April 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28433926/discredited-legacy-stigma-and-familial-amyloid-polyneuropathy-in-northwestern-portugal
#20
Álvaro Mendes, Liliana Sousa, Jorge Sequeiros, Angus Clarke
RATIONALE: Genetic inherited conditions may result in feelings of stigmatisation, mainly because of visible physical appearance and its transmissibility to offspring. OBJECTIVE: This article reports accounts of stigmatisation from Portuguese patients affected by the inherited neurodegenerative disease, familial amyloid polyneuropathy (FAP), living in the largest cluster of patients worldwide. METHOD: We draw on semi-structured interviews conducted with individuals at-risk or affected by FAP, recruited through the national patients' association, about their experiences of stigmatisation related to the illness...
April 15, 2017: Social Science & Medicine
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