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Parkinson's disease and neuroprotection

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https://www.readbyqxmd.com/read/29334320/human-dopamine-transporter-the-first-implementation-of-a-combined-in-silico-in-vitro-approach-revealing-the-substrate-and-inhibitor-specificities
#1
Teodora Djikic, Yasmina Martí, Francesca Spyrakis, Thorsten Lau, Paolo Benedetti, Gavin Davey, Patrick Schloss, Kemal Yelekci
Parkinson's disease (PD) is characterized by the loss of dopamine-generating neurons in the substantia nigra (SN) and corpus striatum (CS). Current treatments alleviate PD symptoms rather than exerting neuroprotective effect on dopaminergic neurons. New drugs targeting the dopaminergic neurons by specific uptake through the human dopamine transporter (hDAT) could represent a viable strategy for establishing selective neuroprotection. Molecules able to increase the bioactive amount of extracellular dopamine (DA), thereby enhancing and compensating a loss of dopaminergic neurotransmission, and to exert neuroprotective response because of their accumulation in the cytoplasm, are required...
January 15, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29332089/gene-therapy-for-parkinson-s-disease
#2
Vivek Sudhakar, R Mark Richardson
Gene therapy is a clinical tool that may eventually provide therapeutic benefit to patients suffering from movement disorders through a few potential mechanisms: direct correction of the pathogenic mechanism, neuroprotection, neurorestoration or symptom control. The therapeutic mechanism is therefore dependent on knowledge of disease pathogenesis and the required temporal and spatial specificities of gene expression. An additional critical challenge is achieving the most complete transduction of the target structure while avoiding leakage into neighboring regions or perivascular spaces...
2018: Progress in Neurological Surgery
https://www.readbyqxmd.com/read/29329976/therapeutic-potential-of-spinal-glp-1-receptor-signaling
#3
REVIEW
Dongao Zhang, Gang Lv
GLP-1 signaling pathway has been well studied for its role in regulating glucose homeostasis, as well as its beneficial effects in energy and nutrient metabolism. A number of drugs based on GLP-1 have been used to treat type 2 diabetes mellitus. GLP-1R is expressed in multiple organs and numerous experimental studies have demonstrated that GLP-1 signaling pathway exhibits pro-survival functions in various disorders. In the central nervous system, stimulation of GLP-1R produces neuroprotective effects in specific neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease...
January 9, 2018: Peptides
https://www.readbyqxmd.com/read/29329581/microrna-124-regulates-the-expression-of-mekk3-in-the-inflammatory-pathogenesis-of-parkinson-s-disease
#4
Longping Yao, Yongyi Ye, Hengxu Mao, Fengfei Lu, Xiaozheng He, Guohui Lu, Shizhong Zhang
BACKGROUND: Parkinson's disease (PD) is the most prevalent neurodegenerative disorder that is characterised by selective loss of midbrain dopaminergic (DA) neurons. Chronic inflammation of the central nervous system is mediated by microglial cells and plays a critical role in the pathological progression of PD. Brain-specific microRNA-124 (miR-124) expression is significantly downregulated in lipopolysaccharide (LPS)-treated BV2 cells and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD...
January 12, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29327204/neuroprotective-effects-of-filgrastim-in-rotenone-induced-parkinson-s-disease-in-rats-insights-into-its-anti-inflammatory-neurotrophic-and-antiapoptotic-effects
#5
Mariama S Azmy, Esther T Menze, Reem N El-Naga, Mariane G Tadros
All current treatments of Parkinson's disease (PD) focus on enhancing the dopaminergic effects and providing symptomatic relief; however, they cannot delay the disease progression. Filgrastim, a recombinant methionyl granulocyte colony-stimulating factor, demonstrated neuroprotection in many neurodegenerative and neurological diseases. This study aimed to assess the neuroprotective effects of filgrastim in rotenone-induced rat model of PD and investigate the potential underlying mechanisms of filgrastim actions...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29318974/-understanding-the-role-of-hypoxia-inducible-factor-during-neurodegeneration-for-new-therapeutics-opportunities
#6
Amalia Merelli, Julio Cesar Garcia Rodriguez, Jaume Folch, Marcelo R Regueiro, Antoni Camins, Lazarowski Alberto
Neurodegeneration (NDG) is linked with the progressive loss of neural function with intellectual and/or motor impairment. Several diseases affecting older individuals, including Alzheimer's disease, Amyotrophic Lateral Sclerosis, Huntington's disease, Parkinson's disease, stroke, Multiple Sclerosis and many others, are the most relevant disorders associated with NDG. Since other pathologies such as refractory epilepsy, brain infections, or hereditary diseases such as "neurodegeneration with brain iron accumulation", also lead to chronic brain inflammation with loss of neural cells, NDG can be said to affect all ages...
January 10, 2018: Current Neuropharmacology
https://www.readbyqxmd.com/read/29315561/faim2-contributes-to-neuroprotection-by-erythropoietin-in-transient-brain-ischemia
#7
Daniel Komnig, Karen Gertz, Pardes Habib, Kay W Nolte, Tareq Meyer, Marc A Brockmann, Matthias Endres, Birgit Rathkolb, Martin Hrabě de Angelis, Jörg B Schulz, Björn H Falkenburger, Arno Reich
Delayed cell death in the penumbra region of acute ischemic stroke occurs through apoptotic mechanisms, making it amenable to therapeutic interventions. Fas/CD95 mediates apoptotic cell death in response to external stimuli. In mature neurons, Fas/CD95 signaling is modulated by Fas-apoptotic inhibitory molecule 2 (Faim2), which reduces cell death in animal models of stroke, meningitis, and Parkinson disease. Erythropoietin (EPO) has been studied as a therapeutic strategy in ischemic stroke. Erythropoietin stimulates the phosphatidylinositol-3 kinase/Akt (PI3K/Akt) pathway, which regulates Faim2 expression...
January 8, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29307179/comparison-of-adaptive-neuroprotective-mechanisms-of-sulforaphane-and-its-interconversion-product-erucin-in-in-vitro-and-in-vivo-models-of-parkinson-s-disease
#8
Fabiana Morroni, Giulia Sita, Alice Djemil, Massimo D'Amico, Letizia Pruccoli, Giorgio Forti, Patrizia Hrelia, Andrea Tarozzi
Several studies suggest that an increase of glutathione (GSH) through activation of the transcriptional nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in the dopaminergic neurons may be a promising neuroprotective strategy in Parkinson's disease (PD). Among Nrf2 activators, isothiocyanate sulforaphane (SFN), derived from precursor glucosinolate present in Brassica vegetables, has gained attention as a potential neuroprotective compound. Bioavailability studies also suggest the contribution of SFN metabolites, including erucin (ERN), to the neuroprotective effects of SFN...
January 7, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29303606/potential-neuroprotective-and-anti-apoptotic-properties-of-a-long-lasting-stable-analog-of-ghrelin-an-in-vitro-study-using-sh-sy5y-cells
#9
A Popelová, A Kákonová, L Hrubá, J Kuneš, L Maletínská, B Železná
Neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are increasing in prevalence. Currently, there are no effective and specific treatments for these disorders. Recently, positive effects of the orexigenic hormone ghrelin on memory and learning were demonstrated in mouse models of AD and PD. In this study, we tested the potential neuroprotective properties of a stable and long-lasting ghrelin analog, Dpr(3)ghrelin (Dpr(3)ghr), in SH-SY5Y neuroblastoma cells stressed with 1...
January 5, 2018: Physiological Research
https://www.readbyqxmd.com/read/29298852/serum-caffeine-and-metabolites-are-reliable-biomarkers-of-early-parkinson-disease
#10
Motoki Fujimaki, Shinji Saiki, Yuanzhe Li, Naoko Kaga, Hikari Taka, Taku Hatano, Kei-Ichi Ishikawa, Yutaka Oji, Akio Mori, Ayami Okuzumi, Takahiro Koinuma, Shin-Ichi Ueno, Yoko Imamichi, Takashi Ueno, Yoshiki Miura, Manabu Funayama, Nobutaka Hattori
OBJECTIVE: To investigate the kinetics and metabolism of caffeine in serum from patients with Parkinson disease (PD) and controls using liquid chromatography-mass spectrometry. METHODS: Levels of caffeine and its 11 metabolites in serum from 108 patients with PD and 31 age-matched healthy controls were examined by liquid chromatography-mass spectrometry. Mutations in caffeine-associated genes were screened by direct sequencing. RESULTS: Serum levels of caffeine and 9 of its downstream metabolites were significantly decreased even in patients with early PD, unrelated to total caffeine intake or disease severity...
January 3, 2018: Neurology
https://www.readbyqxmd.com/read/29291419/neuroprotective-effect-of-olfactory-ensheathing-cells-co-transfected-with-nurr1-and-ngn2-in-both-in-vitro-and-in-vivo-models-of-parkinson-s-disease
#11
Qingqing Liu, Qi Qin, Hongxue Sun, Di Zhong, Ran An, Yushuang Tian, Hongping Chen, Jing Jin, Haining Wang, Guozhong Li
AIMS: The aim of the study is to evaluate the neuroprotective effects of olfactory ensheathing cells (OECs) with the overexpression of nuclear receptor-related factor 1 (Nurr1) and neurogenin 2 (Ngn2) in experimental models of Parkinson's disease (PD) and to elucidate the potential mechanism underlying the neuroprotective effects of OECs-Nurr1-Ngn2. MATERIALS AND METHODS: In vitro study, OECs-Nurr1-Ngn2 conditioned medium (CM) was added to MPP+-treated PC12 cells for 24h, and then the viability of PC12 cells, oxidative stress and apoptosis were detected...
December 29, 2017: Life Sciences
https://www.readbyqxmd.com/read/29290984/estrogen-receptor-activation-contributes-to-rnf146-expression-and-neuroprotection-in-parkinson-s-disease-models
#12
Hyojung Kim, Sangwoo Ham, Joon Yeop Lee, Areum Jo, Gum Hwa Lee, Yun-Song Lee, MyoungLae Cho, Heung-Mook Shin, Donghoon Kim, Olga Pletnikova, Juan C Troncoso, Joo-Ho Shin, Yun-Il Lee, Yunjong Lee
RNF146 is an E3 ubiquitin ligase that specifically recognizes and polyubiquitinates poly (ADP-ribose) (PAR)-conjugated substrates for proteasomal degradation. RNF146 has been shown to be neuroprotective against PAR polymerase-1 (PARP1)-induced cell death during stroke. Here we report that RNF146 expression and RNF146 inducers can prevent cell death elicited by Parkinson's disease (PD)-associated and PARP1-activating stimuli. In SH-SY5Y cells, RNF146 expression conferred resistance to toxic stimuli that lead to PARP1 activation...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29285094/neuroprotective-effects-of-astragaloside-iv-on-parkinson-disease-models-of-mice-and-primary-astrocytes
#13
Lei Xia, Dianxuan Guo, Bing Chen
Parkinson's disease (PD) is characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. Inflammation and neural degeneration are implicated in the pathogenesis of PD. Astragaloside IV (AS-IV) has been verified to attenuate inflammation. The current study aimed to investigate the role of AS-IV in PD and the possible molecular mechanisms. Pole, traction and swim tests were performed to examine the effects of AS-IV on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-generated behavioral deficiencies in vivo...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29281977/n-n-disubstituted-azines-attenuate-lps-mediated-neuroinflammation-in-microglia-and-neuronal-apoptosis-via-inhibiting-mapk-signaling-pathways
#14
Lalita Subedi, Oh Wook Kwon, Chaeho Pak, Goeun Lee, Kangwoo Lee, Hakwon Kim, Sun Yeou Kim
BACKGROUND: Activated microglia interact with astrocytes and neuronal cells to induce neuroinflammation, which can contribute to the pathogenesis and progression of Alzheimer's and Parkinson's disease. To identify the most effective anti-neuroinflammatory agent, we designed and synthesized a family of 13 new azine derivatives and investigated their anti-neuroinflammatory activities in LPS-activated BV-2 microglial cells. RESULTS: Out of 13 derivatives, compound 3 [4,4'-(1E,1'E,3E,3'E)-3,3'-(hydrazine-1,2-diylidene) bis-(prop-1-ene-1-yl-3-ylidene) bis-(2-methoxyphenol)] exhibited excellent anti-neuroinflammatory activities (IC50 = 12...
December 28, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/29277488/ghrelin-mediated-neuroprotection-a-possible-therapy-for-parkinson-s-disease
#15
REVIEW
Alwena H Morgan, Daniel J Rees, Zane B Andrews, Jeffrey S Davies
Parkinson's disease is a common age-related neurodegenerative disorder affecting 10 million people worldwide, but the mechanisms underlying its pathogenesis are still unclear. The disease is characterised by dopamine nerve cell loss in the mid-brain and intra-cellular accumulation of α-synuclein that results in motor and non-motor dysfunction. In this review, we discuss the neuroprotective effects of the stomach hormone, ghrelin, in models of Parkinson's disease. Recent findings suggest that it may modulate mitochondrial function and autophagic clearance of impaired organelle in response to changes in cellular energy balance...
December 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29276478/application-of-the-physical-disector-principle-for-quantification-of-dopaminergic-neuronal-loss-in-a-rat-6-hydroxydopamine-nigral-lesion-model-of-parkinson-s-disease
#16
Katrine Fabricius, Pernille Barkholt, Jacob Jelsing, Henrik H Hansen
Stereological analysis is the optimal tool for quantitative assessment of brain morphological and cellular changes induced by neurotoxic lesions or treatment interventions. Stereological methods based on random sampling techniques yield unbiased estimates of particle counts within a defined volume, thereby providing a true quantitative estimate of the target cell population. Neurodegenerative diseases involve loss of specific neuron types, such as the midbrain tyrosine hydroxylase-positive dopamine neurons in Parkinson's disease and in animal models of nigrostriatal degeneration...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/29273397/pathological-histone-acetylation-in-parkinson-s-disease-neuroprotection-and-inhibition-of-microglial-activation-through-sirt-2-inhibition
#17
Ian F Harrison, Andrew D Smith, David T Dexter
Parkinson's disease (PD) is associated with degeneration of nigrostriatal neurons due to intracytoplasmic inclusions composed predominantly of a synaptic protein called α-synuclein. Accumulations of α-synuclein are thought to 'mask' acetylation sites on histone proteins, inhibiting the action of histone acetyltransferase (HAT) enzymes in their equilibrium with histone deacetylases (HDACs), thus deregulating the dynamic control of gene transcription. It is therefore hypothesised that the misbalance in the actions of HATs/HDACs in neurodegeneration can be rectified with the use of HDAC inhibitors, limiting the deregulation of transcription and aiding neuronal homeostasis and neuroprotection in disorders such as PD...
December 19, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29260495/caffeic-acid-phenethyl-ester-cape-protects-pc12-cells-from-cisplatin-induced-neurotoxicity-by-activating-the-ngf-signaling-pathway
#18
Rafaela Scalco Ferreira, Neife Aparecida Guinaim Dos Santos, Nádia Maria Martins, Laís Silva Fernandes, Antonio Cardozo Dos Santos
Cisplatin is a highly effective chemotherapeutic drug that is toxic to the peripheral nervous system. Findings suggest that axons are early targets of the neurotoxicity of cisplatin. Although many compounds have been reported as neuroprotective, there is no effective treatment against the neurotoxicity of cisplatin. Caffeic acid phenethyl ester (CAPE) is a propolis component with neuroprotective potential mainly attributed to antioxidant and anti-inflammatory mechanisms. We have recently demonstrated the neurotrophic potential of CAPE in a cellular model of neurotoxicity related to Parkinson's disease...
December 19, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29260454/neuroprotective-effect-of-treadmill-exercise-possibly-via-regulation-of-lysosomal-degradation-molecules-in-mice-with-pharmacologically-induced-parkinson-s-disease
#19
Dong-Joo Hwang, Jung-Hoon Koo, Ki-Cheon Kwon, Dong-Hoon Choi, Sung-Deuk Shin, Jae-Hoon Jeong, Hyun-Seob Um, Joon-Yong Cho
Dysfunction of mitophagy, which is a selective degradation of defective mitochondria for quality control, is known to be implicated in the pathogenesis of Parkinson's disease (PD). However, how treadmill exercise (TE) regulates mitophagy-related molecules in PD remains to be elucidated. Therefore, we aimed to investigate how TE regulates α-synuclein (α-syn)-induced neurotoxicity and mitophagy-related molecules in the nigro-striatal region of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mice. Our data showed that TE exhibited a significant restoration of tyrosine hydroxylase and motor coordination with suppression of α-syn expression, hallmarks of PD, possibly via up-regulation of lysosomal degradation molecules, LAMP-2 and cathepsin L, with down-regulation of p62, LC3-II/LC3-I ratio, PINK1 and parkin in the substantia nigra of MPTP mice...
December 19, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/29259548/differential-effects-of-parkinson-s-disease-on-interneuron-subtypes-within-the-human-anterior-olfactory-nucleus
#20
Isabel Ubeda-Bañon, Alicia Flores-Cuadrado, Daniel Saiz-Sanchez, Alino Martinez-Marcos
Synucleinopathies (including α-synucleinopathies), which include Parkinson's disease (PD), manifest themsevles early on (stage 1) in the olfactory system; preferentially in the anterior olfactory nucleus (AON). In particular, the non-motor, early manifestations of PD include hyposmia, which is the partial loss of the sense of smell. The neural basis of hyposmia in PD, however, is poorly understood; but the AON appears to be a key structure in the disease's progression. We analyzed whether α-synuclein was involved in the differential interneuron vulnerability associated with PD in the retrobulbar, cortical anterior and cortical posterior divisions of the AON...
2017: Frontiers in Neuroanatomy
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