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https://www.readbyqxmd.com/read/28096359/%C3%AE-synuclein-binds-and-sequesters-pike-l-into-lewy-bodies-triggering-dopaminergic-cell-death-via-ampk-hyperactivation
#1
Seong Su Kang, Zhentao Zhang, Xia Liu, Fredric P Manfredsson, Li He, P Michael Iuvone, Xuebing Cao, Yi E Sun, Lingjing Jin, Keqiang Ye
The abnormal aggregation of fibrillar α-synuclein in Lewy bodies plays a critical role in the pathogenesis of Parkinson's disease. However, the molecular mechanisms regulating α-synuclein pathological effects are incompletely understood. Here we show that α-synuclein binds phosphoinositide-3 kinase enhancer L (PIKE-L) in a phosphorylation-dependent manner and sequesters it in Lewy bodies, leading to dopaminergic cell death via AMP-activated protein kinase (AMPK) hyperactivation. α-Synuclein interacts with PIKE-L, an AMPK inhibitory binding partner, and this action is increased by S129 phosphorylation through AMPK and is decreased by Y125 phosphorylation via Src family kinase Fyn...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096037/the-future-is-here-but-there-is-no-reason-to-fear
#2
Nicole Fisher
Nicole Fisher, MPP, PhD, is the founder and chief executive officer at HHR Strategies, a health care and human rights focused advising firm. Additionally, she is a senior policy advisor and expert on health economics, technology, and reform, specifically as they affect vulnerable populations. Nicole runs a health innovation and policy page at Forbes, highlighting and advising companies, ideas, and people that are changing the health landscape. She also is currently pursuing her PhD at the University of North Carolina in the Health Policy and Management Department...
February 2017: Surgery
https://www.readbyqxmd.com/read/28093876/development-of-poly-lactide-co-glycolide-nanoparticles-functionalized-with-a-mitochondria-penetrating-peptide
#3
Francesca Selmin, Giulia Magri, Chiara G M Gennari, Silvia Marchianò, Nicola Ferri, Sara Pellegrino
The development of mitochondria-targeting cell permeable vectors represents a promising therapeutic approach for several diseases, such as cancer and oxidative pathologies. Nevertheless, access to mitochondria can be difficult. A new hybrid material composed by poly(lactide-co-glycolide) (PLGA) functionalized with a 6-mer mitochondria penetrating peptide (MPP), consisting in alternating arginine and unnatural cyclohexylalanine, was developed. Circular dichroism, FT-IR and DSC studies indicated that the conjugation of the peptide with the polymer led to the obtainment of a more rigid material with respect to both PLGA and MPP as such...
January 17, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28093210/neuroprotection-by-paeoniflorin-in-the-mptp-mouse-model-of-parkinson-s-disease
#4
Meizhu Zheng, Chunming Liu, Yajun Fan, Pan Yan, Dongfang Shi, Yuchi Zhang
Paeoniflorin (PF) is a major bioactive ingredient in Radix Paeonia alba roots that has low toxicity and has been shown to have neuroprotective effects. Our in vitro experiments suggested that PF affords a significant neuroprotective effect against MPP(+)-induced damage and apoptosis in PC12 cells through Bcl-2/Bax/caspase-3 pathway. The objectives of the present study were to explore the potential neuroprotective effect of PF in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson's disease (PD)...
January 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28070172/summary-of-the-2016-partners-against-mortality-in-epilepsy-pame-conference
#5
(no author information available yet)
Authors: Kevin D Graber, MD, Jeffrey Buchhalter, MD, PhD, Elson So, MD, Rainer Surges, MD, Detlev Boison, PhD, Franck Kalume, PhD, Cyndi Wright, Brian Gehlbach, MD, Jeff Noebels, MD, PhD, Vicky Whittemore, PhD, Elizabeth J. Donner, MD, MSc, Tom Stanton, MPP, Henry Smithson, MD, Jane Hanna, Masud Seyal, MD, PhD, Philippe Ryvlin, MD, PhD The third biannual Partners Against Mortality in Epilepsy (PAME) conference was held in Alexandria, VA from June 23-26, 2016. This was an intimate meeting of clinical and basic scientists, clinicians, people affected by Sudden Unexpected Death in Epilepsy Patients (SUDEP) in a loved one, people living with epilepsy and patient advocate organizations...
November 2016: Epilepsy Currents
https://www.readbyqxmd.com/read/28062948/low-levels-of-prohibitin-in-substantia-nigra-makes-dopaminergic-neurons-vulnerable-in-parkinson-s-disease
#6
Debashis Dutta, Nilufar Ali, Emili Banerjee, Raghavendra Singh, Amit Naskar, Ramesh Kumar Paidi, Kochupurackal P Mohanakumar
Since substantia nigra (SN) and ventral tegmental area (VTA) dopaminergic neurons are, respectively, susceptible or largely unaffected in Parkinson's disease (PD), we searched for protein(s) that regulates this differential sensitivity. Differentially, expressed proteins in SN and VTA were investigated employing two-directional gel electrophoresis- matrix-assisted laser desorption ionization time of flight (MALDI-TOF-TOF) analyses. Prohibitin, which is involved in mitochondrial integrity, was validated using immunoblot, qRT-PCR, and immunohistochemistry in normal mice as well as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-model, PD postmortem human brains, and PD cybrids...
January 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28057814/increased-serum-interleukin-10-but-not-interleukin-4-level-in-children-with-mycoplasma-pneumoniae-pneumonia
#7
Biljana Medjo, Marina Atanaskovic-Markovic, Dimitrije Nikolic, Snezana Radic, Ivana Lazarevic, Ivana Cirkovic, Slobodanka Djukic
BACKGROUND: Mycoplasma pneumoniae (MP) is a common cause of community-acquired pneumonia in children, and it has been associated with wheezing. The aim of this study was to examine the serum level of interleukin (IL)-4 and IL-10 in children with Mycoplasma pneumoniae pneumonia (MPP) and to analyse them in relation to the presence of wheezing. METHODS: The study included 166 children with radiologically confirmed pneumonia. MP infection was confirmed by enzyme-linked immunosorbent assay (ELISA) serum MP-IgM and MP-IgG test and throat swab MP DNA with real-time polymerase chain reaction...
January 5, 2017: Journal of Tropical Pediatrics
https://www.readbyqxmd.com/read/28055011/neuronal-hemoglobin-affects-dopaminergic-cells-response-to-stress
#8
Marta Codrich, Maria Bertuzzi, Roberta Russo, Margherita Francescatto, Stefano Espinoza, Lorena Zentilin, Mauro Giacca, Daniela Cesselli, Antonio Paolo Beltrami, Paolo Ascenzi, Silvia Zucchelli, Francesca Persichetti, Giampiero Leanza, Stefano Gustincich
Hemoglobin (Hb) is the major protein in erythrocytes and carries oxygen (O2) throughout the body. Recently, Hb has been found synthesized in atypical sites, including the brain. Hb is highly expressed in A9 dopaminergic (DA) neurons of the substantia nigra (SN), whose selective degeneration leads to Parkinson's disease (PD). Here we show that Hb confers DA cells' susceptibility to 1-methyl-4-phenylpyridinium (MPP(+)) and rotenone, neurochemical cellular models of PD. The toxic property of Hb does not depend on O2 binding and is associated with insoluble aggregate formation in the nucleolus...
January 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28034780/formononetin-attenuates-a%C3%AE-25-35-induced-cytotoxicity-in-ht22-cells-via-pi3k-akt-signaling-and-non-amyloidogenic-cleavage-of-app
#9
Lizhi Chen, Shanshan Ou, Lingqi Zhou, Hai Tang, Jie Xu, Kaihua Guo
Amyloid beta (Aβ) is the main component of the amyloid plaques that accumulate in the brains of Alzheimer patients. Here, we reported the protective role of Formononetin (Form) against Aβ25-35-induced neurotoxicity in HT22 cells. We found that Form significantly increased the viability of HT22 cells but decreased the cell apoptosis when challenging with Aβ25-35. The inhibitory effects of Form were associated with PI3K/Akt signaling pathway as PI3K inhibitor (LY294002) or ERα specific inhibitor (MPP) blocked the effects...
December 26, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/28031767/mechanical-differences-between-barbell-and-body-optimum-power-loads-in-the-jump-squat-exercise
#10
Irineu Loturco, Lucas A Pereira, Vinicius Zanetti, Katia Kitamura, César C Cal Abad, Ronaldo Kobal, Fabio Y Nakamura
This study compared the values of bar-peak force (PFBar) and power (PPBar), body-peak force (PFBody) and power (PPBody) and bar-mean propulsive power (MPPBar) in different jump-squat (JS) conditions: unloaded condition (UC); bar-loaded condition (BLC) and optimum bar-MPP condition (OBC). Twenty-five soccer players performed the JS using a bar with negligible mass (UC), using the Smith-machine bar (BLC) and using the load capable of maximizing the bar-MPP (OBC). The PFBody was significantly higher in the UC (2847...
December 1, 2016: Journal of Human Kinetics
https://www.readbyqxmd.com/read/28027699/two-new-compounds-from-atractylodes-macrocephala-with-neuroprotective-activity
#11
Na Zhang, Chao Liu, Tie-Min Sun, Xiao-Ku Ran, Ting-Guo Kang, De-Qiang Dou
In the present study, two new compounds, together with six known compounds, were isolated from rhizome of Atractylodes macrocephala Koidz by a series of silica gel, ODS column chromatography, and preparative HPLC. Their structures were characterized as atractylenolide II (1), atractylenolide I (2), biepiasterolid (3), isoatractylenolide I (4), atractylenolide III (5), 3β-acetoxyl atractylenolide I (6), (4E,6E,12E)-tetradeca-4,6,12-triene-8,10-diyne-13,14-triol (7), (3S,4E,6E,12E)-1-acetoxy-tetradeca-4,6,12-triene-8,10-diyne-3,14-diol (8) on the basis of 1D, 2D NMR, and circular dichroism analyses...
January 2017: Journal of Asian Natural Products Research
https://www.readbyqxmd.com/read/28025231/cardiac-resynchronization-therapy-by-multipoint-pacing-improves-response-of-left-ventricular-mechanics-and-fluid-dynamics-a-three-dimensional-and-particle-image-velocimetry-echo-study
#12
Mariachiara Siciliano, Federico Migliore, Luigi Badano, Emanuele Bertaglia, Gianni Pedrizzetti, Stefano Cavedon, Alessandro Zorzi, Domenico Corrado, Sabino Iliceto, Denisa Muraru
AIMS: To characterize the effect of multipoint pacing (MPP) compared to biventricular pacing (BiV) on left ventricle (LV) mechanics and intraventricular fluid dynamics by three-dimensional echocardiography (3DE) and echocardiographic particle imaging velocimetry (Echo-PIV). METHODS AND RESULTS: In 11 consecutive patients [8 men; median age 65 years (57-75)] receiving cardiac resynchronization therapy (CRT) with a quadripolar LV lead (Quartet,St.Jude Medical,Inc...
December 26, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28018301/screening-and-identification-of-apoc1-as-a-novel-potential-biomarker-for-differentiate-of-mycoplasma-pneumoniae-in-children
#13
Jieqiong Li, Lin Sun, Fang Xu, Hui Qi, Chen Shen, Weiwei Jiao, Jing Xiao, Qinjing Li, Baoping Xu, Adong Shen
Background: Although Mycoplasma pneumoniae (MP) is a common cause of community-acquired pneumonia (CAP) in children, the currently used diagnostic methods are not optimal. Proteomics is increasingly being used to study the biomarkers of infectious diseases. Methods: Label-free quantitative proteomics and liquid chromatography-mass/mass spectrometry were used to analyze the fold change of protein expression in plasma of children with MP pneumonia (MPP), infectious disease control (IDC), and healthy control (HC) groups...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28018211/cistanche-tubulosa-protects-dopaminergic-neurons-through-regulation-of-apoptosis-and-glial-cell-derived-neurotrophic-factor-in-vivo-and-in-vitro
#14
Qian Xu, Wen Fan, Shui-Fen Ye, Yi-Bo Cong, Wei Qin, Shi-Ya Chen, Jing Cai
Parkinson's disease (PD) is a neurodegenerative disease with the pathological hallmark of reduced nigrostriatal dopamine. In traditional Chinese medicine (TCM) clinical practice, the nanopowder of Cistanche tubulosa has therapeutic effects on PD. To identify the therapeutic mechanism, this study tested the protective effect of different doses of MPP(+)-induced toxicity in MES23.5 cells using the MTT assay and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice (vehicles). Immunohistochemistry was used to assess cytomorphology and tyrosine hydroxylase (TH) expression...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27993520/overexpression-of-%C3%AE-camkii-impairs-behavioral-flexibility-and-nmdar-dependent-long-term-depression-in-the-dentate-gyrus
#15
Pengcheng Yin, Hao Xu, Qi Wang, Jiayue Wang, Liang Yin, Meichen Xu, Zhenyang Xie, Wenzhao Liu, Xiaohua Cao
Behavioral flexibility is in close proximity to dentate gyrus (DG) function and long-term depression (LTD), but the role of DG LTD in behavioral flexibility has hitherto been unexplored. Although the functions of alpha-Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) have been studied extensively, the role of βCaMKII, a constituent of the CaMKII holoenzyme, in LTD and behavioral flexibility has not been investigated in vivo. Here using the βCaMKII-F90G transgenic (TG) mice, in which the inducible and reversible overexpression of βCaMKII is restricted to dentate gyrus (DG), we found that TG mice exhibited defective behavioral flexibility in two reversal tasks and seriously impaired N-methyl-d-aspartic acid receptor (NMDAR)-dependent LTD in DG medial perforant path (MPP)...
December 16, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27977936/potent-inhibition-of-human-organic-cation-transporter-2-hoct2-by-%C3%AE-carboline-alkaloids
#16
David J Wagner, Haichuan Duan, Alenka Jaklic, Richard W Lee, Joanne Wang
1. Beta-carbolines are indole alkaloids with a wide range of pharmacological and toxicological activities. Beta-carbolines are structurally related to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+), a known substrate of organic cation transporters (OCTs). The goal of this study is to determine the interaction of β-carbolines with human OCT1, 2, and 3 (SLC22A1-3). 2. Dose-dependent inhibition studies were performed for five commercially available β-carbolines using a fluorescent substrate assay in HEK293 cells stably expressing hOCT1-3...
December 15, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27960106/aldose-reductase-deficiency-leads-to-oxidative-stress-induced-dopaminergic-neuronal-loss-and-autophagic-abnormality-in-an-animal-model-of-parkinson-s-disease
#17
Patrick K K Yeung, Angela K W Lai, Hyo Jin Son, Xu Zhang, Onyou Hwang, Stephen S M Chung, Sookja K Chung
Fungicide exposure causes degeneration of dopaminergic neurons and contributes to Parkinson's disease (PD). Benomyl inhibits enzymes responsible for detoxifying the reactive dopamine metabolite 3,4-dihydroxyphenylacetaldehyde. Aldose reductase (AR) is known as tetrahydrobiopterin (BH4) reductase that generates BH4, a cofactor for tyrosine hydroxylase (TH) involved in dopamine synthesis. AR also acts as an aldehyde reductase involved in detoxifying 3,4-dihydroxyphenylacetaldehyde. In PD patients, the level of AR is significantly lower in the cerebellum...
February 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/27958349/metabolite-profiling-of-preneoplastic-and-neoplastic-lesions-of-oral-cavity-tissue-samples-revealed-a-biomarker-pattern
#18
Syed Ghulam Musharraf, Najia Shahid, Syed Muhammad Ali Naqvi, Mahwish Saleem, Amna Jabbar Siddiqui, Anwar Ali
Oral cancer is a major health challenge in the Indian subcontinent and a dreadful form of cancers worldwide. The current study is focused on the identification of distinguished metabolites of oral cancer tissue samples in comparison with precancerous and control tissue samples using gas chromatography coupled with triple quadrupole tandem mass spectrometry and chemometric analyses. Metabolites obtained were identified through National Institute of Standards and Technology (NIST) mass spectral (Wiley registry) library...
December 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27957685/trpm2-promotes-neurotoxin-mpp-mptp-induced-cell-death
#19
Yuyang Sun, Pramod Sukumaran, Senthil Selvaraj, Nicholas I Cilz, Anne Schaar, Saobo Lei, Brij B Singh
In neurons, Ca(2+) is essential for a variety of physiological processes that regulate gene transcription to neuronal growth and their survival. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium ions (MPP(+)) are potent neurotoxins that selectively destroys the dopaminergic (DA) neurons and mimics Parkinson's disease (PD) like symptoms, but the mechanism as how MPP(+)/MPTP effects DA neuron survival is not well-understood. In the present study, we found that MPP(+) treatment increased the level of reactive oxygen species (ROS) that activates and upregulates the expression and function of melastatin-like transient receptor potential (TRPM) subfamily member, melastatin-like transient receptor potential channel 2 (TRPM2)...
December 12, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27956836/relationships-between-th1-th2-cytokine-profiles-and-chest-radiographic-manifestations-in-childhood-mycoplasma-pneumoniae-pneumonia
#20
Jiu-Ling Zhao, Xin Wang, Yu-Shui Wang
BACKGROUND: Mycoplasma pneumoniae pneumonia (MPP) is one of the most common childhood community-acquired pneumonias, and the chest radiograph usually shows bronchial pneumonia, segmental/lobar pneumonia, or segmental/lobar pneumonia with pleural effusion. The imbalance of Th1/Th2 function after Mycoplasma pneumoniae infection is an important immunological mechanism of MPP. In this study, we aimed to evaluate the correlations between Th1/Th2 cytokine profiles and chest radiographic manifestations in MPP children...
2016: Therapeutics and Clinical Risk Management
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