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https://www.readbyqxmd.com/read/28429857/ndufa4l2-protects-against-ischemia-reperfusion-induced-cardiomyocyte-apoptosis-and-mitochondrial-dysfunction-by-inhibiting-complex-i
#1
Jianhua Li, Caiyan Bai, Junxia Guo, Wanqian Liang, Jingning Long
Myocardial ischemia/reperfusion (I/R) injury may cause the apoptosis of cardiomyocytes as well as mitochondrial dysfunction. The aims of the present study were to investigate whether NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) on myocardial ischemia-reperfusion (I/R) injury and the underlying molecular mechanism. The hypoxia-reperfusion (H/R) model was established in vitro using H9c2 cells to simulate I/R injury. NDUFA4L2 and complex I expression levels were detected using RT-PCR and western blot...
April 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28428752/desensitizing-mitochondrial-permeability-transition-by-erk-cyclophilin-d-axis-contributes-to-the-neuroprotective-effect-of-gallic-acid-against-cerebral-ischemia-reperfusion-injury
#2
Jing Sun, Da-Dui Ren, Jin-Yi Wan, Chen Chen, Dong Chen, Huan Yang, Chun-Lai Feng, Jing Gao
Ischemic stroke is a devastating disease with complex pathophysiology. Much evidence confirms that opening of the mitochondrial permeability transition pore (MPTP) is related with mitochondrial dysfunction to apoptosis in ischemic stroke, thus elucidating its signaling mechanism and screening novel MPTP inhibitor is therefore of paramount importance. Our earlier studies identified that gallic acid (GA), a naturally occurring plant phenol, endows with effect on inhibition of mitochondrial dysfunction, which has significant neuroprotective effect in cerebral ischemia/reperfusion injury...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28424060/effects-of-a-combination-treatment-of-kd5040-and-l-dopa-in-a-mouse-model-of-parkinson-s-disease
#3
Sora Ahn, Taek-Jin Song, Seong-Uk Park, Songhee Jeon, Jongpil Kim, Joo-Young Oh, Jaehwan Jang, Sanhwa Hong, Min-A Song, Hye-Seoung Shin, Young-Rim Jung, Hi-Joon Park
BACKGROUND: Although the dopamine precursor L-3, 4-dihydroxyphenylalanine ( l -dopa) remains the gold standard pharmacological therapy for patients with Parkinson's disease (PD), long-term treatment with this drug has been known to result in several adverse effects, including l -dopa-induced dyskinesia (LID). Recently, our group reported that KD5040, a modified herbal remedy, had neuroprotective effects in both in vitro and in vivo models of PD. Thus, the present study investigated whether KD5040 would have synergistic effects with l -dopa and antidyskinetic effects caused by l -dopa as well...
April 19, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28420545/gqsar-modeling-and-combinatorial-library-generation-of-4-phenylquinazoline-2-carboxamide-derivatives-as-antiproliferative-agents-in-human-glioblastoma-tumors
#4
Debolina Goswami, Sukriti Goyal, Salma Jamal, Ritu Jain, Divya Wahi, Abhinav Grover
BACKGROUND: TSPO translocator protein, encoded in humans by the Tspo gene plays a crucial role in mitochondria mediated apoptosis and necrotic cell death through its association with Mitochondrial Permeability Transition pore (MPTP). It has been shown that this function can be exploited as a potential treatment for human Glioblastoma Multiforme. In this study, a novel robust fragment based QSAR model has been developed for a series of 4-phenylquinazoline-2-carboxamides experimentally known to be ligands for TSPO, thus triggering apoptotic mechanism cascade...
April 4, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28411054/salidroside-protects-rat-liver-against-ischemia-reperfusion-injury-by-regulating-the-gsk-3%C3%AE-nrf2-dependent-antioxidant-response-and-mitochondrial-permeability-transition
#5
Linlin Cai, Yonghua Li, Qingqing Zhang, Haijing Sun, Xiaodi Yan, Tong Hua, Qiufeng Zhu, Haitao Xu, Hailong Fu
Salidroside (Sal) is a natural antioxidant that elicits cardioprotective and neuroprotective effects in vivo and in vitro; however, its impact on hepatic ischemia/reperfusion (I/R) injury remains unclear. The purpose of this study was to investigate the hepatoprotective effects of salidroside against segmental (70%) warm hepatic I/R injury in rats. Animals were randomized into Sham, Sham+salidroside pretreatment (Sal), Sham+Sal+carboxyatractyloside (CATR), Sham+CATR, I/R, I/R+Sal, I/R+Sal+CATR and I/R+CATR groups...
April 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28409819/spermicidal-efficacy-of-vrp-a-synthetic-cationic-antimicrobial-peptide-inducing-apoptosis-and-membrane-disruption
#6
Prasanta Ghosh, Arpita Bhoumik, Sudipta Saha, Sandipan Mukherjee, Sarfuddin Azmi, Jimut Kanti Ghosh, Sandhya Rekha Dungdung
Presently available contraceptives are mostly hormonal or detergent in nature with numerous side effects like irritation, lesion, inflammation in vagina, alteration of body homeostasis etc. Antimicrobial peptides with spermicidal activity but without adverse effects may be suitable alternatives. In the present study spermicidal activity of a cationic antimicrobial peptide VRP on human spermatozoa has been elucidated. Progressive forward motility of human spermatozoa was instantly stopped after 100 µM VRP treatment and at 350 µM all kinds of sperm motility ceased within 20 seconds as assessed by the Sander-Cramer assay...
April 14, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28407688/npc-26-kills-human-colorectal-cancer-cells-via-activating-ampk-signaling
#7
Zhen Zhao, Li Feng, Jiqin Wang, Deshan Cheng, Mei Liu, Meirong Ling, Weiping Xu, Keyu Sun
NPC-26 is novel mitochondrion-interfering compound. The current study tested its potential effect against colorectal cancer (CRC) cells. We demonstrated that NPC-26 induced potent anti-proliferative and cytotoxic activities against CRC cell lines (HCT-116, DLD-1 and HT-29). Activation of AMP-activated protein kinase (AMPK) signaling mediated NPC-26-induced CRC cell death. AMPKα1 shRNA knockdown or dominant negative mutation abolished NPC-26-induced AMPK activation and subsequent CRC cell death. NPC-26 disrupted mitochondrial function, causing mitochondrial permeability transition pore (mPTP) opening and reactive oxygen species (ROS) production...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400118/pre-clinical-therapeutic-development-of-a-series-of-metalloporphyrins-for-parkinson-s-disease
#8
Li-Ping Liang, Jie Huang, Ruth Fulton, Jennifer N Pearson-Smith, Brian J Day, Manisha Patel
Reactive oxygen species are a well-defined therapeutic target for Parkinson's disease (PD) and pharmacological agents that catalytically scavenge reactive species are promising neuroprotective strategies for treatment. Metalloporphyrins are synthetic catalytic antioxidants that mimic the body's own antioxidant enzymes i.e. superoxide dismutases and catalase. The goal of this study was to determine if newly designed metalloporphyrins have enhanced pharmacodynamics including oral bioavailability, longer plasma elimination half-lives, penetrate the blood brain barrier, and show promise for PD treatment...
April 8, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28398674/melatonin-protects-cardiac-microvasculature-against-ischemia-reperfusion-injury-via-suppression-of-mitochondrial-fission-vdac1-hk2-mptp-mitophagy-axis
#9
Hao Zhou, Ying Zhang, Shunying Hu, Chen Shi, Pingjun Zhu, Qiang Ma, Qinhua Jin, Feng Cao, Feng Tian, Yundai Chen
The cardiac microvascular system, which is primarily composed of monolayer endothelial cells, is the site of blood supply and nutrient exchange to cardiomyocytes. However, microvascular ischemia/reperfusion injury (IRI) following percutaneous coronary intervention is a woefully neglected topic and few strategies are available to reverse such pathologies. Here, we studied the effects of melatonin on microcirculation IRI and elucidated the underlying mechanism. Melatonin markedly reduced infarcted area, improved cardiac function, restored blood flow and lower microcirculation perfusion defects...
April 11, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28395670/absence-of-physiological-ca-2-transients-is-an-initial-trigger-for-mitochondrial-dysfunction-in-skeletal-muscle-following-denervation
#10
Chehade Karam, Jianxun Yi, Yajuan Xiao, Kamal Dhakal, Lin Zhang, Xuejun Li, Carlo Manno, Jiejia Xu, Kaitao Li, Heping Cheng, Jianjie Ma, Jingsong Zhou
BACKGROUND: Motor neurons control muscle contraction by initiating action potentials in muscle. Denervation of muscle from motor neurons leads to muscle atrophy, which is linked to mitochondrial dysfunction. It is known that denervation promotes mitochondrial reactive oxygen species (ROS) production in muscle, whereas the initial cause of mitochondrial ROS production in denervated muscle remains elusive. Since denervation isolates muscle from motor neurons and deprives it from any electric stimulation, no action potentials are initiated, and therefore, no physiological Ca(2+) transients are generated inside denervated muscle fibers...
April 10, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28390981/neurochemical-effects-of-the-r-form-of-%C3%AE-lipoic-acid-and-its-neuroprotective-mechanism-in-cellular-models-of-parkinson-s-disease
#11
Hong Zhao, Xingcheng Zhao, Lijuan Liu, Hongxu Zhang, Mingwen Xuan, Zhaohui Guo, Hongcai Wang, Chang Liu
OBJECTIVE: Parkinson's disease (PD) is a common neurodegenerative disease. This study aimed to investigate the effects of the R form of α-lipoic acid (RLA) in cellular models of PD induced by 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). METHODS: Cell viability and apoptosis were detected using CCK8 and Annexin V-FITC assays, respectively. Intracellular reactive oxygen species (ROS) were detected by fluorescence staining. ELISA assays were performed to detect the levels of dopamine and α-synuclein...
April 5, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28386306/a-preclinical-systematic-review-of-ginsenoside-rg1-in-experimental-parkinson-s-disease
#12
REVIEW
Liang Song, Meng-Bei Xu, Xiao-Li Zhou, Dao-Pei Zhang, Shu-Ling Zhang, Guo-Qing Zheng
To date, no drug has been proven to be neuroprotective or disease-modifying for Parkinson's disease (PD) in clinical trials. Here, we aimed to assess preclinical evidence of Ginsenosides-Rg1 (G-Rg1), a potential neuroprotectant, for experimental PD and its possible mechanisms. Eligible studies were identified by searching six electronic databases from their inception to August 2016. Twenty-five eligible studies involving 516 animals were identified. The quality score of these studies ranged from 3 to 7. Compared with the control group, two out of the 12 studies of MPTP-induced PD showed significant effects of G-Rg1 for improving the rotarod test (P < 0...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28385921/the-effects-of-physical-exercise-on-non-motor-symptoms-and-on-neuroimmune-rage-network-in-experimental-parkinsonism
#13
Sofia D Viana, Inês R Pita, Cristina Lemos, Daniel Rial, Patrícia Couceiro, Paulo Rodrigues-Santos, Francisco Caramelo, Félix Carvalho, Syed F Ali, Rui D Prediger, Carlos A Fontes Ribeiro, Frederico C Pereira
Parkinson's disease (PD) prodromic stages comprise neuropsychiatric perturbations that critically compromise patient's quality of life. These non-motor symptoms (NMS) are associated with exacerbated innate immunity, a hallmark of overt PD. Physical exercise (PE) has the potential to improve neuropsychiatric deficits and to modulate immune network including receptors for advanced glycation endproducts (RAGE) and Toll-like receptors (TLRs) in distinct pathological settings. Accordingly, the present study aimed to test the hypothesis that PE i) alleviates PD NMS and ii) modulates neuroimmune RAGE-network in experimental PD...
April 6, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28382410/structural-and-functional-state-of-erythrocyte-membranes-in-mice-at-different-stages-of-experimental-parkinson-s-disease-induced-by-administration-of-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-mptp
#14
L D Fatkullina, E M Molochkina, A I Kozachenko, L G Nagler, E B Burlakova
We studied some structural and functional parameters of erythrocyte membranes in mice at the late presymptomatic and early symptomatic stages of experimental Parkinson's disease induced by administration of MPTP (hemolysis, microviscosity of different regions of the lipid bilayer, LPO intensity, activity of antioxidant enzymes, and kinetic properties of acetylcholinesterase). At the presymptomatic stage, significant deviations of the studied parameters from the normal were observed; they were similar in direction and magnitude to those in humans with Parkinson's disease...
November 1, 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28380329/changes-in-blood-anti-oxidation-enzyme-levels-in-mptp-treated-monkeys
#15
Like Li, Liangqin Shi, Heng Liu, Qihui Luo, Chao Huang, Wentao Liu, Xiaolin Chen, Wen Zeng, Zhengli Chen
Oxidative stress has been implicated in a range of neurodegenerative diseases, in particular, Parkinson's disease (PD). However, the pathogenic mechanism of its influence on PD progression remains unclear. In order to clarify this, PD models are generated by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intramuscular injection in eight rhesus monkeys. During the of progress PD pathogenesis, the activities of some major antioxidant enzymes, such as serum superoxide dismutase (SOD), glutathione peroxidase (GPX), and glutathione-s-transferase (GST), were measured, which show continuously decrease...
April 2, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28377118/single-low-doses-of-mptp-decrease-tyrosine-hydroxylase-expression-in-the-absence-of-overt-neuron-loss
#16
Gelareh Alam, Melissa Edler, Shelbie Burchfield, Jason R Richardson
Parkinson's disease (PD) is the second most common age-related neurodegenerative disease. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a prototypical neurotoxicant used in mice to mimic primary features of PD pathology including striatal dopamine depletion and dopamine neuron loss in the substantia nigra pars compacta (SNc). In the literature, there are several experimental paradigms involving multiple doses of MPTP that are used to elicit dopamine neuron loss. However, a recent study reported that a single low dose caused significant loss of dopamine neurons...
April 1, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28373075/recovery-from-experimental-parkinsonism-by-intrastriatal-application-of-erythropoietin-or-epo-releasing-neural-precursors
#17
Stephana Carelli, Toniella Giallongo, Cristina Viaggi, Elisa Latorre, Zuzana Gombalova, Andrea Raspa, Massimiliano Mazza, Francesca Vaglini, Anna Maria Di Giulio, Alfredo Gorio
An extensive literature has shown a powerful neuroprotective action of Erythropoietin (EPO) both in vivo and in vitro. This study shows that EPO, whether ectopically administered or released by neural precursors, does reverse MPTP-induced parkinsonism in mice. Unilateral stereotaxic injection of 2.5 × 10(5) erythropoietin-releasing neural precursor cells (Er-NPCs) rescued degenerating striatal dopaminergic neurons and promoted behavioral recovery as shown by three independent behavioral tests. These effects were replicated through direct intrastriatal administration of recombinant human EPO...
April 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28369799/effect-of-dental-pulp-stem-cells-in-mptp-induced-old-aged-mice-model
#18
Nareshwaran Gnanasegaran, Vijayendran Govindasamy, Christopher Simon, Quan Fu Gan, Vui King Vincent-Chong, Vasudevan Mani, Kesavanarayanan Krishnan Selvarajan, Vellayan Subramaniam, Sabri Musa, Noor Hayaty Abu Kasim
Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic (DA-ergic) neurons in the substantia nigra (SN) and represent as a huge threat to the geriatric population. Cell-replacement therapies (CRTs) have been proposed as a promising strategy to slow down or replace neuronal loss. Among the widely available cell sources, dental pulp stem cells (DPSCs) portray as an attractive source primarily due to their neural crest origin, ease of tissue procurement and less ethical hurdles MATERIALS AND METHODS: We first demonstrated the in vitro differentiation ability of DPSCs towards DA-ergic-like cells before evaluating their neuro-protection/neuro-restoration capacities in MPTP-induced mice...
March 30, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28369131/liver-x-receptors-activation-through-to901317-binding-reduces-neuroinflammation-in-parkinson-s-disease
#19
Irene Paterniti, Michela Campolo, Rosalba Siracusa, Marika Cordaro, Rosanna Di Paola, Vittorio Calabrese, Michele Navarra, Salvatore Cuzzocrea, Emanuela Esposito
Parkinson's disease (PD) is a neurodegenerative disease in which degeneration of nigrostriatal neurons and inflammation are key players. The aim of our study was to analyze the function of LXRs in neurodegenerative diseases as PD using in vivo, ex vivo and in vitro models of PD; for this purpose, we observed the effects of the LXR agonist, TO901317, in neuroinflammatory pathway related to PD. We performed an in vivo model of PD using the neurotoxin 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP) and our results clearly showed that TO901317 administration reduces all of the inflammatory markers involved in PD such as iNOS and COX2, IκB-α and NF-κB...
2017: PloS One
https://www.readbyqxmd.com/read/28366809/effect-of-d-ala-2-gip-a-stable-gip-receptor-agonist-on-mptp-induced-neuronal-impairments-in-mice
#20
Mahip K Verma, Rajan Goel, Krishnadas Nandakumar, Kumar V S Nemmani
The aim of the present study was to evaluate the ability of D-Ala(2)GIP, a gastric inhibitory polypeptide (GIP) receptor agonist, to attenuate the behavioral phenotype of Parkinson's disease caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in mice. In the behavioral studies, MPTP administration led to spontaneous locomotor activity deficits, impaired rotarod performance, akinesia, muscular rigidity and increased tremor amplitude, which was attenuated by pretreatment with D-Ala(2)GIP (50-100 nmol/kg, i...
March 30, 2017: European Journal of Pharmacology
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