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https://www.readbyqxmd.com/read/28928221/upregulation-of-autophagy-related-gene-5-protects-dopaminergic-neurons-in-a-zebrafish-model-of-parkinson-s-disease
#1
Zhan-Ying Hu, Bo Chen, Jing-Pu Zhang, Yuan-Yuan Ma
Parkinson's disease (PD) is one of the most epidemic neurodegenerative diseases, and is characterized by movement disorders arising from loss of midbrain dopaminergic (DA) neurons. Recently, the relationship between PD and autophagy has received considerable attention, but information about the mechanisms involved is lacking. Here, we report that autophagy-related gene 5 (ATG5) is potentially important in protecting dopaminergic neurons in a 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in zebrafish...
September 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28926343/the-impact-of-stress-on-social-behavior-in-adult-zebrafish-danio-rerio
#2
Shannon M Saszik, Conor M Smith
Stress has adverse effects on social behavior that is mediated by dopamine circuits in the midbrain. The purpose of this research is to examine the effect of chronic stress and dopamine signals on social behavior in zebrafish (Danio rerio). Chronic stress was induced chemically with low dosage of ethanol (0.25% for 5 days), and psychosocially with isolation (3-5 days) or overcrowding (5 days). Dopamine activity was decreased by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure. Social behavior was observed by introducing one treated zebrafish to a group of four control zebrafish and measuring the nearest neighbor distance (NND)...
September 18, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28922345/tilianin-post-conditioning-attenuates-myocardial-ischemia-reperfusion-injury-via-mitochondrial-protection-and-inhibition-of-apoptosis
#3
Yangyang Wang, Yong Yuan, Xinchun Wang, Yanfang Wang, Jiang Cheng, Li Tian, Xinhong Guo, Dongmei Qin, Wenjiang Cao
BACKGROUND The aim of this study was to investigate the role of tilianin in modulating mitochondrial functions and mitochondria-mediated apoptosis during cardio-protection. MATERIAL AND METHODS Myocardial ischemia/reperfusion (I/R) injury was induced by 30 minutes coronary occlusion followed by two hours reperfusion in Sprague-Dawley rats. To investigate the cardio-protective effects of tilianin, apoptosis was evaluated by TUNEL. Mitochondrial ultrastructure and function were assessed by transmission electron microscopy, dynamics of mitochondrial permeability transition pore (mPTP) opening and ATP production in the myocardium; Ca2+ content and reactive oxygen species (ROS) were measured to evaluated the level of damage factors in the mitochondria...
September 18, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28917506/the-plasmalogen-precursor-analog-ppi-1011-reduces-the-development-of-l-dopa-induced-dyskinesias-in-de-novo-mptp-monkeys
#4
Mélanie Bourque, Laurent Grégoire, Thérèse Di Paolo
The gold standard therapy for Parkinson's disease (PD), L-3,4-dihydroxyphenylalanine (L-DOPA), induces dyskinesias in the majority of patients after years of treatment. Ethanolamine plasmalogens (PlsEtn) play critical roles in membrane structure mediated functions and as a storage depot of polyunsaturated fatty acids such as docosahexaenoic acid. We previously showed that a PlsEtn precursor PPI-1011 reduced already established L-DOPA-induced dyskinesias (LID) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioned monkeys as a PD model...
September 13, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28913661/discovery-of-non-peptidic-small-molecule-inhibitors-of-cyclophilin-d-as-neuroprotective-agents-in-a%C3%AE-induced-mitochondrial-dysfunction
#5
Insun Park, Ashwini M Londhe, Ji Woong Lim, Beoung-Geon Park, Seo Yun Jung, Jae Yeol Lee, Sang Min Lim, Kyoung Tai No, Jiyoun Lee, Ae Nim Pae
Cyclophilin D (CypD) is a mitochondria-specific cyclophilin that is known to play a pivotal role in the formation of the mitochondrial permeability transition pore (mPTP).The formation and opening of the mPTP disrupt mitochondrial homeostasis, cause mitochondrial dysfunction and eventually lead to cell death. Several recent studies have found that CypD promotes the formation of the mPTP upon binding to β amyloid (Aβ) peptides inside brain mitochondria, suggesting that neuronal CypD has a potential to be a promising therapeutic target for Alzheimer's disease (AD)...
September 14, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28912345/a-novel-bibenzyl-compound-20c-protected-mice-from-mptp-p-toxicity-by-regulating-alpha-synuclein-related-inflammatory-response
#6
Qiu-Shuang Zhang, Yang Heng, Ying Chen, Piao Luo, Lu Wen, Zhao Zhang, Yu-He Yuan, Nai-Hong Chen
The novel bibenzyl compound 20C plays a neuroprotective role in vitro, but its effects in vivo have not been elucidated. In this study, we estimated the efficacy of 20C in vivo using a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine/probenecid (MPTP/p) mouse model from behavior, dopamine and neuron, and then the possible mechanisms for these effects were further investigated. The experimental results showed that 20C improved behavioral deficits, attenuated dopamine depletion, reduced dopaminergic neuron loss, protected blood brain barrier structure, ameliorated α-synuclein dysfunction, suppressed glial activation, and regulated both NF-κB signaling and the NLRP3 inflammasome pathway...
September 14, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28906548/activation-of-g-protein-coupled-estrogen-receptor-1-at-the-onset-of-reperfusion-protects-the-myocardium-against-ischemia-reperfusion-injury-by-reducing-mitochondrial-dysfunction-and-mitophagy
#7
Yansheng Feng, Ngonidzashe B Madungwe, Carolina Victoria da Cruz Junho, Jean C Bopassa
BACKGROUND AND PURPOSE: Recent evidence indicates that Gper1 (G Protein-coupled Estrogen Receptor 1) mediates acute pre-ischemic estrogen-induced protection of the myocardium from ischemia/reperfusion injury via a signaling cascade that includes PKC translocation, ERK1/2 /GSK-3β phosphorylation and the inhibition of the mitochondrial permeability transition pore (mPTP) opening. Here, we investigated the impact and mechanism involved in post-ischemic Gper1 activation in ischemia/reperfusion injury...
September 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28902711/triggering-of-inflammasome-by-impaired-autophagy-in-response-to-acute-experimental-parkinson-s-disease-involvement-of-the-pi3k-akt-mtor-pathway
#8
Sabrina Giacoppo, Placido Bramanti, Emanuela Mazzon
Several lines of evidence suggest that the inflammasome activation is involved in the progression of neurodegenerative diseases. However, the relation between Parkinson's disease (PD) and the inflammasome is still unclear. This study was designed to assess the involvement of inflammasome in acute experimental PD. Specifically, acute PD was induced in C57BL/6 mice by an injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). At seven days from MPTP induction, mice were euthanized and the midbrains were sampled to carry out immunohistochemical evaluations and western blot analysis...
September 11, 2017: Neuroreport
https://www.readbyqxmd.com/read/28881606/gsk1059615-kills-head-and-neck-squamous-cell-carcinoma-cells-possibly-via-activating-mitochondrial-programmed-necrosis-pathway
#9
Jing Xie, Quan Li, Xi Ding, Yunyun Gao
This study tested the anti-head and neck squamous cell carcinoma (HNSCC) cell activity by GSK1059615, a novel PI3K and mTOR dual inhibitor. GSK1059615 inhibited survival and proliferation of established (SCC-9, SQ20B and A253 lines) and primary human HNSCC cells. GSK1059615 blocked PI3K-AKT-mTOR activation in HNSCC cells. Intriguingly, GSK1059615 treatment in HNSCC cells failed to provoke apoptosis, but induced programmed necrosis. The latter was tested by mitochondria depolarization, ANT-1-cyclophilin-D mitochondrial association and lactate dehydrogenase (LDH) release...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877690/gypenosides-ameliorate-memory-deficits-in-mptp-lesioned-mouse-model-of-parkinson-s-disease-treated-with-l-dopa
#10
Ting Ting Zhao, Kyung Sook Kim, Keon Sung Shin, Hyun Jin Park, Hyun Jeong Kim, Kyung Eun Lee, Myung Koo Lee
BACKGROUND: Previous studies have revealed that gypenosides (GPS) improve the symptoms of anxiety disorders in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned rat model of Parkinson's disease (PD). The present study aimed to investigate the effects of GPS on memory deficits in an MPTP-lesioned mouse model of PD treated with L-3,4-dihydroxyphenylalanine (L-DOPA). METHODS: MPTP (30 mg/kg/day, 5 days)-lesioned mice were treated with GPS (50 mg/kg) and/or L-DOPA (10 and 25 mg/kg) for 21 days...
September 6, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28877102/treadmill-exercise-modifies-dopamine-receptor-expression-in-the-prefrontal-cortex-of-the-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-lesioned-mouse-model-of-parkinson-s-disease
#11
Natalie Kintz, Giselle M Petzinger, Michael W Jakowec
Parkinson's disease (PD) is the second most common neurodegenerative disorder for which there is no cure. PD is a dopamine (DA)-deficit disorder marked by progressive motor and nonmotor disturbances, including cognitive impairment. Executive function (EF) is the most common subtype of cognitive impairment in PD and consists of deficits in number of processes including behavioral flexibility. The prefrontal cortex (PFC) is an important brain region subserving EF. Furthermore, DA plays a key neuromodulatory role in the PFC and altered DA neurotransmission is believed to contribute toward EF deficits in PD...
September 4, 2017: Neuroreport
https://www.readbyqxmd.com/read/28875428/timed-release-of-cerebrolysin-using-drug-loaded-titanate-nanospheres-reduces-brain-pathology-and-improves-behavioral-functions-in-parkinson-s-disease
#12
Asya Ozkizilcik, Aruna Sharma, Dafin F Muresanu, José V Lafuente, Z Ryan Tian, Ranjana Patnaik, Herbert Mössler, Hari S Sharma
Previous studies from our laboratory show that intraperitoneal injections of 1-metyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP, 20 mg/kg) daily within 2-h intervals for 5 days in mice induce Parkinson's disease (PD)-like symptoms on the 8th day. A significant decrease in dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) along with a marked decrease in the number of tyrosine hydroxylase (TH)-positive cells in the substantia nigra pars compacta (SNpc) and striatum (STr) confirms the validity of this model for studying PD...
September 5, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28874733/mitochondrial-permeability-transition-pore-sensitivity-to-opening-and-mechanistic-dependence-on-substrate-availability
#13
Thomas Briston, Malcolm Roberts, Sian Lewis, Ben Powney, James M Staddon, Gyorgy Szabadkai, Michael R Duchen
Mitochondrial Ca(2+) uptake has a key role in cellular Ca(2+) homeostasis. Excessive matrix Ca(2+) concentrations, especially when coincident with oxidative stress, precipitate opening of an inner mitochondrial membrane, high-conductance channel: the mitochondrial permeability transition pore (mPTP). mPTP opening has been implicated as a final cell death pathway in numerous diseases and therefore understanding conditions dictating mPTP opening is crucial for developing targeted therapies. Here, we have investigated the impact of mitochondrial metabolic state on the probability and consequences of mPTP opening...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28874678/mitochondrial-cyclophilin-d-ablation-is-associated-with-the-activation-of-akt-p70s6k-pathway-in-the-mouse-kidney
#14
Jelena Klawitter, Alexander Pennington, Jost Klawitter, Joshua M Thurman, Uwe Christians
The mitochondrial matrix protein cyclophilin D (CypD) is an essential component of the mitochondrial permeability transition pore (MPTP). Here we characterized the effects of CypD ablation on bioenergetics in the kidney. CypD loss triggers a metabolic shift in Ppif-/- male and female mouse kidneys towards glycolysis and Krebs cycle activity. The shift is accompanied by increased glucose consumption and a transcriptional upregulation of effectors of glucose metabolism in the kidney. These included activation of Akt, AMPK (only in males) and p70S6K kinases...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28866799/intranasal-administration-of-tat-conjugated-lipid-nanocarriers-loading-gdnf-for-parkinson-s-disease
#15
Sara Hernando, Enara Herran, Joana Figueiro-Silva, José Luis Pedraz, Manoli Igartua, Eva Carro, Rosa Maria Hernandez
Parkinson's disease (PD) is the second most common neurodegenerative disorder (ND), characterized by the loss of dopaminergic neurons, microglial activation, and neuroinflammation. Current available treatments in clinical practice cannot halt the progression of the disease. During the last few years, growth factors (GFs) have been raised as a promising therapeutic approach to address the underlying neurodegenerative process. Among others, glial cell-derived neurotrophic factor (GDNF) is a widely studied GF for PD...
September 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28864907/alterations-in-the-reduced-pteridine-contents-in-the-cerebrospinal-fluids-of-lrrk2-mutation-carriers-and-patients-with-parkinson-s-disease
#16
Hiroshi Ichinose, Ken-Ichi Inoue, Shinobu Arakawa, Yuki Watanabe, Hiroki Kurosaki, Shoko Koshiba, Eldbjorg Hustad, Masahiko Takada, Jan O Aasly
Tetrahydrobiopterin (BH4) is a cofactor for tyrosine hydroxylase that is essential for the biosynthesis of dopamine. Parkinson's disease (PD) is characterized by a progressive degeneration of nigrostriatal dopaminergic neurons, and biomarkers reflecting the degree of neurodegeneration are important not only for basic research but also for clinical diagnosis and the treatment of the disease. Although the total neopterin and biopterin levels in the cerebrospinal fluids (CSF) of the patients with PD were reported, alterations in the composition of reduced and oxidized forms of pteridine compounds have not been examined...
September 1, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28862602/-the-effect-of-neurotoxin-mptp-administration-to-mice-on-the-proteomic-profile-of-brain-isatin-binding-proteins
#17
O A Buneeva, A T Kopylov, L N Nerobkova, I G Kapitsa, V G Zgoda, A E Medvedev
Isatin (indole-2,3-dione) is an endogenous indole found in the mammalian brain, peripheral organs and body fluids. It acts as a neuroprotector, which decreases manifestation of locomotor impairments in animal models of Parkinson's disease. A wide range of biological activity of isatin is associated with interaction of this regulator with numerous isatin-binding proteins. The aim of this study was to investigate the profile of brain isatin-binding proteins in mice with MPTP-induced Parkinsonism (90 min and seven days after administration of this neurotoxin)...
July 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28861737/chronic-mptp-administration-regimen-in-monkeys-a-model-of-dopaminergic-and-non-dopaminergic-cell-loss-in-parkinson-s-disease
#18
REVIEW
Gunasingh J Masilamoni, Yoland Smith
Parkinson's disease (PD) is a progressive neurodegenerative disorder clinically characterized by cardinal motor deficits including bradykinesia, tremor, rigidity and postural instability. Over the past decades, it has become clear that PD symptoms extend far beyond motor signs to include cognitive, autonomic and psychiatric impairments, most likely resulting from cortical and subcortical lesions of non-dopaminergic systems. In addition to nigrostriatal dopaminergic degeneration, pathological examination of PD brains, indeed, reveals widespread distribution of intracytoplasmic inclusions (Lewy bodies) and death of non-dopaminergic neurons in the brainstem and thalamus...
August 31, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28858313/human-ips-cell-derived-dopaminergic-neurons-function-in-a-primate-parkinson-s-disease-model
#19
Tetsuhiro Kikuchi, Asuka Morizane, Daisuke Doi, Hiroaki Magotani, Hirotaka Onoe, Takuya Hayashi, Hiroshi Mizuma, Sayuki Takara, Ryosuke Takahashi, Haruhisa Inoue, Satoshi Morita, Michio Yamamoto, Keisuke Okita, Masato Nakagawa, Malin Parmar, Jun Takahashi
Induced pluripotent stem cells (iPS cells) are a promising source for a cell-based therapy to treat Parkinson's disease (PD), in which midbrain dopaminergic neurons progressively degenerate. However, long-term analysis of human iPS cell-derived dopaminergic neurons in primate PD models has never been performed to our knowledge. Here we show that human iPS cell-derived dopaminergic progenitor cells survived and functioned as midbrain dopaminergic neurons in a primate model of PD (Macaca fascicularis) treated with the neurotoxin MPTP...
August 30, 2017: Nature
https://www.readbyqxmd.com/read/28854243/antiparkinsonian-effects-of-the-radiprodil-and-tozadenant-combination-in-mptp-treated-marmosets
#20
Anne Michel, Jean-Marie Nicolas, Sarah Rose, Michael Jackson, Peter Colman, Willy Briône, David Sciberras, Pierandrea Muglia, Dieter K Scheller, Martin Citron, Patrick Downey
OBJECTIVE: Investigate a combination of two clinically tested drugs, the NR2B antagonist Radiprodil and the A2A antagonist Tozadenant in the MPTP-treated marmoset model of Parkinson's Disease (PD). BACKGROUND: In PD, there remains a need for the development of non-dopaminergic drugs to effectively treat the motor symptoms without the induction of L-Dopa-induced motor complications. METHODS: Clinically relevant doses of Radiprodil and Tozadenant were given both alone and in combination without the addition of L-Dopa, and the antiparkinsonian efficacy of the treatments was assessed in a primate model of PD...
2017: PloS One
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