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https://www.readbyqxmd.com/read/28338241/neuroprotective-effects-of-loganin-on-mptp-induced-parkinson-s-disease-mice-neurochemistry-glial-reaction-and-autophagy-studies
#1
Yi-Da Xu, Chun Cui, Meng-Fei Sun, Ying-Li Zhu, Min Chu, Yun-Wei Shi, Stanley Li Lin, Xu-Sheng Yang, Yan-Qin Shen
Parkinson's disease (PD) is a progressive neurodegenerative disease, involving resting tremor and bradykinesia, for which no recognized therapies or drugs are available to halt or slow progression. In recent years, natural botanic products have been considered relatively safe, with limited side effects, and are expected to become an important source for clinical mediation of PD in the future. Our study focuses on the ability of loganin, a compound derived from fruits of cornus, to mediate neuroprotection in a mouse model of PD...
March 24, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28337124/interleukin-4-protects-dopaminergic-neurons-in-vitro-but-is-dispensable-for-mptp-induced-neurodegeneration-in-vivo
#2
Laura Hühner, Jennifer Rilka, Ralf Gilsbach, Xiaolai Zhou, Venissa Machado, Björn Spittau
Microglia are involved in physiological as well as neuropathological processes in the central nervous system (CNS). Their functional states are often referred to as M1-like and M2-like activation, and are believed to contribute to neuroinflammation-mediated neurodegeneration or neuroprotection, respectively. Parkinson's disease (PD) is one the most common neurodegenerative disease and is characterized by the progressive loss of midbrain dopaminergic (mDA) neurons in the substantia nigra resulting in bradykinesia, tremor, and rigidity...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28334043/cc-223-blocks-mtorc1-c2-activation-and-inhibits-human-hepatocellular-carcinoma-cells-in-vitro-and-in-vivo
#3
Zichen Xie, Jiqin Wang, Mei Liu, Deshan Chen, Chao Qiu, Keyu Sun
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related human mortalities. Over-activation of mammalian target of rapamycin (mTOR) is important for HCC tumorigenesis and progression. The current study assessed the potential anti-HCC activity by a novel mTOR kinase inhibitor, CC-223. We demonstrate that CC-223, at nM concentrations, induced profound cytotoxic and anti-proliferative activities against established HCC cell lines (HepG2, KYN-2 and Huh-7) and primary human HCC cells. Meanwhile, CC-223 activated caspase-3/-9 and apoptosis in the above HCC cells...
2017: PloS One
https://www.readbyqxmd.com/read/28332824/indole-substituted-benzothiazoles-and-benzoxazoles-as-selective-and-reversible-mao-b-inhibitors-for-treatment-of-parkinson-s-disease
#4
Min-Ho Nam, Moosung Park, Hyeri Park, Youngjae Kim, Seulki Yoon, Vikram Shahaji Sawant, Ji Won Choi, Jong-Hyun Park, Ki Duk Park, Sun-Joon Min, Changjoon Justin Lee, Hyunah Choo
To develop a novel, selective, and reversible MAO-B inhibitors for safer treatment of Parkinson's disease, benzothiazole and benzoxazole derivatives with indole moiety were designed and synthesized. Most of the synthesized compounds showed inhibitory activities against MAO-B and selectivity over MAO-A. The most active compound was Compound 5b, 6-fluoro-2-(1-methyl-1H-indol-5-yl)benzo[d]thiazole with an IC50 value of 29 nM with no apparent effect on MAO-A activity at 10 M. Based on the reversibility assay, Compound 5b turned out to be a fully reversible with over 95% of recovery of enzyme activity after washout of the compound...
March 23, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28324237/cyclosporine-a-induces-endoplasmic-reticulum-stress-and-influences-pro-apoptotic-factors-in-human-gingival-fibroblasts
#5
Suresh Ranga Rao, Shiyamali Sundararajan, Rajasekaran Subbarayan, Dinesh Murugan Girija
Cyclosporine-A (CsA) induces gingival overgrowth. Cyclosporine's anti-apoptotic activity in human gingival fibroblast is due to desensitization of mitochondrial permeability transition pore (MPTP) and augmentation of anti-apoptotic, Bcl2. Alternative mechanisms of apoptosis exist involving enzymes like calcium-dependent Calpain and signaling events related to apoptosis, like Glycogen synthase kinase 3β (GSK3β) and protein kinase A (PKA). Cyclosporine-A in renal tubular cells induces endoplasmic reticulum stress (ER stress) which has not been explored in gingival overgrowth...
March 21, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28322751/neuroprotective-effects-of-2-4-dinitrophenol-in-an-acute-model-of-parkinson-s-disease
#6
Yujeong Lee, Gwangbeom Heo, Kyung Moon Lee, Ah Hyun Kim, Ki Wung Chung, Eunok Im, Hae Young Chung, Jaewon Lee
Neurons depend on mitochondria for homeostasis and survival, and thus, mitochondrial dysfunction has been implicated in neurodegenerative diseases, including Parkinson's disease (PD). Increasing evidence indicates the mitochondrial uncoupler, 2,4-dinitrophenol (DNP), protects neurons against neurodegeneration and enhances neural plasticity. Here, the authors evaluated the protective effects of intraperitoneally (i.p.) administered low dose DNP in an acute mouse model of PD. Mice were administered DNP (1 or 5 mg/kg) for 12 consecutive days, and then on day 13, MPTP (20 mg/kg, i...
March 17, 2017: Brain Research
https://www.readbyqxmd.com/read/28321769/n-propargyl-caffeamide-paca-ameliorates-dopaminergic-neuronal-loss-and-motor-dysfunctions-in-mptp-mouse-model-of-parkinson-s-disease-and-in-mpp-induced-neurons-via-promoting-the-conversion-of-prongf-to-ngf
#7
Dan Luo, Jia Zhao, Yuanyuan Cheng, Simon Ming-Yuen Lee, Jianhui Rong
Insufficient production of nerve growth factor (NGF) is implicated in Parkinson's disease (PD). We recently discovered that caffeic acid derivative N-propargyl caffeamide (PACA) not only potentiated NGF-induced neurite outgrowth but also attenuated 6-hydroxydopamine neurotoxicity in neuronal culture. The aim of the present study was to investigate whether PACA could increase NGF levels against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) neurotoxicity in a mouse PD model. We induced parkinsonism in mice by intraperitoneal injection of MPTP for seven consecutive days...
March 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28320442/analysis-of-monocyte-infiltration-in-mptp-mice-reveals-that-microglial-cx3cr1-protects-against-neurotoxic-over-induction-of-monocyte-attracting-ccl2-by-astrocytes
#8
Vincent R Parillaud, Guillaume Lornet, Yann Monnet, Anne-Laure Privat, Andrei T Haddad, Vanessa Brochard, Amaury Bekaert, Camille Baudesson de Chanville, Etienne C Hirsch, Christophe Combadière, Stéphane Hunot, Christian S Lobsiger
BACKGROUND: Evidence from mice suggests that brain infiltrating immune cells contribute to neurodegeneration, and we previously identified a deleterious lymphocyte infiltration in Parkinson's disease mice. However, this remains controversial for monocytes, due to artifact-prone techniques used to distinguish them from microglia. Our aim was to reassess this open question, by taking advantage of the recent recognition that chemokine receptors CCR2 and CX3CR1 can differentiate between inflammatory monocytes and microglia, enabling to test whether CCR2(+) monocytes infiltrate the brain during dopaminergic (DA) neurodegeneration and whether they contribute to neuronal death...
March 21, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28320274/brain-mitochondrial-subproteome-of-rpn10-binding-proteins-and-its-changes-induced-by-the-neurotoxin-mptp-and-the-neuroprotector-isatin
#9
A E Medvedev, O A Buneeva, A T Kopylov, O V Tikhonova, M V Medvedeva, L N Nerobkova, I G Kapitsa, V G Zgoda
Mitochondria play an important role in molecular mechanisms of neuroplasticity, adaptive changes of the brain that occur in the structure and function of its cells in response to altered physiological conditions or development of pathological disorders. Mitochondria are a crucial target for actions of neurotoxins, causing symptoms of Parkinson's disease in various experimental animal models, and also neuroprotectors. Good evidence exists in the literature that mitochondrial dysfunction induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) influences functioning of the ubiquitin-proteasomal system (UPS) responsible for selective proteolytic degradation of proteins from various intracellular compartments (including mitochondria), and neuroprotective effects of certain antiparkinsonian agents (monoamine oxidase inhibitors) may be associated with their effects on UPS...
March 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28317877/transcription-factor-nf-kappa-b-represses-ant1-transcription-and-leads-to-mitochondrial-dysfunctions
#10
Chen Zhang, Hui Jiang, Pin Wang, Heng Liu, Xiulian Sun
Mitochondria are intracellular organelles involved in cell survival and death, and dysfunctions of mitochondria are related to neurodegenerative diseases. As the most abundant protein in the mitochondrial inner membrane, adenine nucleotide translocator 1 (ANT1) plays a critical role in mitochondrial function, including the exchange of adenosine triphosphate/adenosine diphosphate (ATP/ADP) in mitochondria, basal proton leak and mitochondrial permeability transition pore (mPTP). Here, we show that ANT1 transcription is regulated by transcription factor NF-kappa B (NF-κB)...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28304399/chemical-profiling-analysis-of-maca-using-uhplc-esi-orbitrap-ms-coupled-with-uhplc-esi-qqq-ms-and-the-neuroprotective-study-on-its-active-ingredients
#11
Yanyan Zhou, Peng Li, Adelheid Brantner, Hongjie Wang, Xinbin Shu, Jian Yang, Nan Si, Lingyu Han, Haiyu Zhao, Baolin Bian
Lepidium meyenii (Maca), originated from Peru, has been cultivated widely in China as a popular health care food. However, the chemical and effective studies of Maca were less in-depth, which restricted its application seriously. To ensure the quality of Maca, a feasible and accurate strategy was established. One hundred and sixty compounds including 30 reference standards were identified in 6 fractions of methanol extract of Maca by UHPLC-ESI-Orbitrap MS. Among them, 15 representative active compounds were simultaneously determined in 17 samples by UHPLC-ESI-QqQ MS...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28299414/photobiomodulation-induced-changes-in-a-monkey-model-of-parkinson-s-disease-changes-in-tyrosine-hydroxylase-cells-and-gdnf-expression-in-the-striatum
#12
Nabil El Massri, Ana P Lemgruber, Isobel J Rowe, Cécile Moro, Napoleon Torres, Florian Reinhart, Claude Chabrol, Alim-Louis Benabid, John Mitrofanis
Intracranial application of red to infrared light, known also as photobiomodulation (PBM), has been shown to improve locomotor activity and to neuroprotect midbrain dopaminergic cells in rodent and monkey models of Parkinson's disease. In this study, we explored whether PBM has any influence on the number of tyrosine hydroxylase (TH)(+)cells and the expression of GDNF (glial-derived neurotrophic factor) in the striatum. Striatal sections of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated mice and monkeys and 6-hydroxydopamine (6OHDA)-lesioned rats that had PBM optical fibres implanted intracranially (or not) were processed for immunohistochemistry (all species) or western blot analysis (monkeys)...
March 15, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28292971/selective-replacement-of-mitochondrial-dna-increases-cardioprotective-effect-of-chronic-continuous-hypoxia-in-spontaneously-hypertensive-rats
#13
Jan Neckar, Anna Svatonova, Romana Weissova, Zdenek Drahota, Pavlina Zajickova, Iveta Brabcova, David Kolar, Petra Alanova, Jana Vasinova, Jan Silhavy, Marketa Hlavackova, Katerina Tauchmannova, Marie Milerova, Bohuslav Ostadal, Ludek Cervenka, Jitka Zurmanova, Martin Kalous, Olga Novakova, Jiri Novotny, Michal Pravenec, Frantisek Kolar
Mitochondria play an essential role in improved cardiac ischemic tolerance conferred by adaptation to chronic hypoxia. In the present study, we analyzed effects of continuous normobaric hypoxia (CNH) on mitochondrial functions, including the sensitivity of mitochondrial permeability transition pore (MPTP) to opening, and infarct size in hearts of spontaneously hypertensive rats (SHR) and in conplastic SHR-mtBN strain characterized by the selective replacement of the mitochondrial genome of SHR with that of more ischemia-resistant Brown Norway (BN) strain...
March 14, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28290500/pramipexole-restores-depressed-transmission-in-the-ventral-hippocampus-following-mptp-lesion
#14
Javier Castro-Hernández, Paul A Adlard, David I Finkelstein
The hippocampus has a significant association with memory, cognition and emotions. The dopaminergic projections from both the ventral tegmental area and substantia nigra are thought to be involved in hippocampal activity. To date, however, few studies have investigated dopaminergic innervation in the hippocampus or the functional consequences of reduced dopamine in disease models. Further complicating this, the hippocampus exhibits anatomical and functional differentiation along its dorso-ventral axis. In this work we investigated the role of dopamine on hippocampal long term potentiation using D-amphetamine, which stimulates dopamine release, and also examined how a dopaminergic lesion affects the synaptic transmission across the anatomic subdivisions of the hippocampus...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28288978/mff-dependent-mitochondrial-fission-contributes-to-the-pathogenesis-of-cardiac-microvasculature-ischemia-reperfusion-injury-via-induction-of-mros-mediated-cardiolipin-oxidation-and-hk2-vdac1-disassociation-involved-mptp-opening
#15
Hao Zhou, Shunying Hu, Qinhua Jin, Chen Shi, Ying Zhang, Pingjun Zhu, Qiang Ma, Feng Tian, Yundai Chen
BACKGROUND: The cardiac microvascular system ischemia/reperfusion injury following percutaneous coronary intervention is a clinical thorny problem. This study explores the mechanisms by which ischemia/reperfusion injury induces cardiac microcirculation collapse. METHODS AND RESULTS: In wild-type mice, mitochondrial fission factor (Mff) expression increased in response to acute microvascular ischemia/reperfusion injury. Compared with wild-type mice, homozygous Mff-deficient (Mff(gt)) mice exhibited a smaller infarcted area, restored cardiac function, improved blood flow, and reduced microcirculation perfusion defects...
March 13, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28282815/the-mptp-story
#16
J William Langston
No abstract text is available yet for this article.
2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28280525/the-short-isoform-of-dnajb6-protects-against-1-methyl-4-phenylpridinium-ion-induced-apoptosis-in-ln18-cells-via-inhibiting-both-ros-formation-and-mitochondrial-membrane-potential-loss
#17
Yeon-Mi Hong, Yohan Hong, Yeong-Gon Choi, Sujung Yeo, Soo Hee Jin, Sae-Won Lee, Backil Sung, Sook-Hyun Lee, Hyejin Jung, Sabina Lim
In a previous study, we found that the short isoform of DNAJB6 (DNAJB6(S)) had been decreased in the striatum of a mouse model of Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). DNAJB6, one of the heat shock proteins, has been implicated in the pathogenesis of PD. In this study, we explored the cytoprotective effect of DNAJB6(S) against 1-methyl-4-phenylpyridinium ion- (MPP(+)-) induced apoptosis and the underlying molecular mechanisms in cultured LN18 cells from astrocytic tumors...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28279753/partial-lesion-of-dopamine-neurons-of-rat-substantia-nigra-impairs-conditioned-place-aversion-but-spares-conditioned-place-preference
#18
Bernardo F C Lima, Daniele C Ramos, Janaína K Barbiero, Laura Pulido, Peter Redgrave, Donita L Robinson, Alexander Gómez-A, Claudio Da Cunha
Midbrain dopamine neurons play critical roles in reward- and aversion-driven associative learning. However, it is not clear whether they do this by a common mechanism or by separate mechanisms that can be dissociated. In the present study we addressed this question by testing whether a partial lesion of the dopamine neurons of the rat SNc has comparable effects on conditioned place preference (CPP) learning and conditioned place aversion (CPA) learning. Partial lesions of dopamine neurons in the rat substantia nigra pars compacta (SNc) induced by bilateral intranigral infusion of 6-hydroxydopamine (6-OHDA, 3μg/side) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 200μg/side) impaired learning of conditioned place aversion (CPA) without affecting conditioned place preference (CPP) learning...
March 7, 2017: Neuroscience
https://www.readbyqxmd.com/read/28279081/persistent-expression-of-dopamine-synthesizing-enzymes-15-years-after-gene-transfer-in-a-primate-model-of-parkinson-s-disease
#19
Yoshihide Sehara, Ken-Ichi Fujimoto, Kunihiko Ikeguchi, Yuko Katakai, Fumiko Ono, Naomi Takino, Mika Ito, Keiya Ozawa, Shin-Ichi Muramatsu
Restoring dopamine production in the putamen through gene therapy is a straightforward strategy for ameliorating motor symptoms for Parkinson's disease (PD). In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity-based primate model of PD, we previously showed the safety and efficacy of adeno-associated virus (AAV) vector-mediated gene delivery to the putamen of three dopamine-synthesizing enzymes (tyrosine hydroxylase [TH], aromatic l-amino acid decarboxylase [AADC], and guanosine triphosphate cyclohydrolase I [GCH]) up to 10 months post-procedure...
March 9, 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28275337/tir-domain-containing-adapter-inducing-interferon-%C3%AE-trif-is-essential-for-mptp-induced-dopaminergic-neuroprotection-via-microglial-cell-m1-m2-modulation
#20
Minghui Shan, Sen Lin, Shurong Li, Yuchen Du, Haixia Zhao, Huarong Hong, Ming Yang, Xi Yang, Yongmei Wu, Liyi Ren, Jiali Peng, Jing Sun, Hongli Zhou, Bingyin Su
Dynamic changes of two phenotypes of microglia, M1 and M2, are critically associated with the neurodegeneration of Parkinson's disease. However, the regulation of the M1/M2 paradigm is still unclear. In the MPTP induced neurodegeneration model, we examined the concentration of dopamine (DA) related metabolites and the survival of tyrosine hydroxylase (TH) positive cells in WT and Trif(-/-) mice. In in vitro experiments, MN9D cells were co-cultured with BV2 cells to mimic the animal experiments. Inhibition of TRIF aggravated TH+ cell loss, and DA-related metabolites decreased...
2017: Frontiers in Cellular Neuroscience
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