المؤلفون: H. Fai Poon, Mark Frasier, Nathan Shreve, Vittorio Calabrese, Benjamin Wolozin, D. Allan Butterfield

المصدر: Neurobiology of Disease, Vol 18, Iss 3, Pp 492-498 (2005)

مصطلحات موضوعية: Parkinson's disease, A30P, Oxidative stress, Lactate dehydrogenase, Enolase, Carbonic anhydrase, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized by the loss of dopaminergic neurons in the substantia nigra compacta. α-Synuclein is strongly implicated in the pathophysiology of PD because aggregated α-synuclein accumulates in the brains of subjects with PD, mutations in α-synuclein cause familial PD, and overexpressing mutant human α-synuclein (A30P or A53T) causes degenerative disease in mice or drosophila. The pathophysiology of PD is poorly understood, but increasing evidence implicates mitochondrial dysfunction and oxidative stress. To understand how mutations in α-synuclein contribute to the pathophysiology of PD, we undertook a proteomic analysis of transgenic mice overexpressing A30P α-synuclein to investigate which proteins are oxidized. We observed more than twofold selective increases in specific carbonyl levels of three metabolic proteins in brains of symptomatic A30P α-synuclein mice: carbonic anhydrase 2 (Car2), alpha-enolase (Eno1), and lactate dehydrogenase 2 (Ldh2). Analysis of the activities of these proteins demonstrates decreased functions of these oxidatively modified proteins in brains from the A30P compared to control mice. Our findings suggest that proteins associated with impaired energy metabolism and mitochondria are particularly prone to oxidative stress associated with A30P-mutant α-synuclein.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S0969996104003201Test; https://doaj.org/toc/1095-953XTest

الوصول الحر: https://doaj.org/article/f2267929dbc44b1297b692ce78da5293Test

المؤلفون: Adelaide Fernandes, Ana S. Falcão, Rui F.M. Silva, D. Allan Butterfield, Maria Alexandra Brito, Dora Brites, Alexandra Isabel Rosa

المساهمون: Repositório da Universidade de Lisboa

المصدر: Neurobiology of Disease, Vol 29, Iss 1, Pp 30-40 (2008)
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP

مصطلحات موضوعية: Cell death, Programmed cell death, Lipid peroxidation, Protein oxidation, medicine.disease_cause, Antioxidants, lcsh:RC321-571, chemistry.chemical_compound, fluids and secretions, Pregnancy, medicine, Animals, Buthionine sulfoximine, Drug Interactions, Rats, Wistar, Cell damage, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Cells, Cultured, chemistry.chemical_classification, Cerebral Cortex, Neurons, Reactive oxygen species, Cell-type vulnerability, Dose-Response Relationship, Drug, L-Lactate Dehydrogenase, Chemistry, Neurotoxicity, Neurosciences, Bilirubin, Glutathione, medicine.disease, Embryo, Mammalian, Cell biology, Acetylcysteine, Rats, Neurology, Biochemistry, nervous system, Astrocytes, embryonic structures, Female, Reactive Oxygen Species, Oxidation-Reduction, Oxidative stress

الوصف: We investigated whether nerve cell damage by unconjugated bilirubin (UCB) is mediated by oxidative stress and ascertained the neuronal and astroglial susceptibility to injury. Several oxidative stress biomarkers and cell death were determined following incubation of neurons and astrocytes isolated from rat cortical cerebrum with UCB (0.01-1.0 microM). We show that UCB induces a dose-dependent increase in neuronal death in parallel with the oxidation of cell components and a decrease in the intracellular glutathione content. Comparison of the results obtained in both cell types demonstrates that neurons are more vulnerable than astrocytes to oxidative injury by UCB, for which accounts the lower glutathione stores in neuronal cells. Moreover, neuronal oxidative injury is prevented by supplementation with N-acetylcysteine, a glutathione precursor, whereas astroglial sensitivity to UCB is enhanced by inhibition of glutathione synthesis, using buthionine sulfoximine. Collectively, we demonstrate that oxidative stress is involved in UCB neurotoxicity and depict a new therapeutic approach for UCB-induced oxidative damage.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::711f0e437ebe7410b7b89ad03b30f0adTest
http://www.sciencedirect.com/science/article/pii/S096999610700174XTest

المؤلفون: Alberto Granzotto, Stefano L. Sensi

المصدر: Neurobiology of Disease, Vol 81, Iss, Pp 25-37 (2015)

مصطلحات موضوعية: inorganic chemicals, Male, N-Methylaspartate, Population, Neuronal death, Excitotoxicity, Glycine, chemistry.chemical_element, nNOS, Nitric Oxide Synthase Type I, Mitochondrion, Calcium, Biology, medicine.disease_cause, Receptors, N-Methyl-D-Aspartate, lcsh:RC321-571, Mice, medicine, Excitatory Amino Acid Agonists, Animals, Overproduction, education, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Cells, Cultured, Membrane Potential, Mitochondrial, Neurons, education.field_of_study, Glutamate receptor, NADPH Dehydrogenase, Extracellular Fluid, Embryo, Mammalian, Corpus Striatum, Cell biology, Mitochondria, Zinc, Neurology, chemistry, Biochemistry, nervous system, Oxidative stress, L-Lactate Dehydrogenase (Cytochrome), Glutamate, Reactive Oxygen Species, Homeostasis

الوصف: Excessive and sustained exposure to glutamate leads to injurious elevations of cytosolic calcium ([Ca(2+)]i), generation of reactive oxygen and nitrogen species (ROS, RNS), mitochondrial failure, mobilization of intracellular zinc ([Zn(2+)]i), and, ultimately, neuronal death. The relative contribution and temporal dynamics of the activation of these processes to promote the full development of excitotoxicity are still not completely understood. In this study, we exploited the unique features of nNOS positive neurons [nNOS (+)], a striatal subpopulation that is constitutively spared from NMDAR-dependent insults, and dissected NMDAR-driven [Ca(2+)]i, [Zn(2+)]i, ROS, and mitochondrial changes occurring in these neurons and the overall population of nNOS (-) striatal neurons. Comparing the two populations and employing pharmacological, biochemical, and single-cell imaging techniques, we show that [Zn(2+)]i mobilization acts as a critical intermediate in the cascade that links NMDAR-mediated ROS overproduction, mitochondrial failure, and [Ca(2+)]i deregulation to the production of neuronal damage. Results of this study may also provide the rationale for aiming at therapeutic agents that favor Zn(2+) homeostasis for the treatment of acute or chronic neurological conditions associated with excitotoxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::983f86bd0caa9d1fc480020f591decc4Test
https://pubmed.ncbi.nlm.nih.gov/25940914Test

المؤلفون: Benjamin Wolozin, Nathan Shreve, Mark Frasier, D. Allan Butterfield, Vittorio Calabrese, H. Fai Poon

المصدر: Neurobiology of Disease, Vol 18, Iss 3, Pp 492-498 (2005)

مصطلحات موضوعية: Genetically modified mouse, Parkinson's disease, Proline, animal diseases, Transgene, Enolase, Synucleins, Mice, Transgenic, Nerve Tissue Proteins, A30P, Biology, Mitochondrion, medicine.disease_cause, lcsh:RC321-571, Mitochondrial Proteins, Mice, chemistry.chemical_compound, Degenerative disease, medicine, Animals, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Alpha-synuclein, Carbonic anhydrase, Alanine, Pars compacta, Lactate dehydrogenase, Brain, Parkinson Disease, medicine.disease, nervous system diseases, Cell biology, Mice, Inbred C57BL, Disease Models, Animal, Oxidative Stress, nervous system, Neurology, chemistry, Biochemistry, alpha-Synuclein, Energy Metabolism, Oxidative stress

الوصف: Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized by the loss of dopaminergic neurons in the substantia nigra compacta. alpha-Synuclein is strongly implicated in the pathophysiology of PD because aggregated alpha-synuclein accumulates in the brains of subjects with PD, mutations in alpha-synuclein cause familial PD, and overexpressing mutant human alpha-synuclein (A30P or A53T) causes degenerative disease in mice or drosophila. The pathophysiology of PD is poorly understood, but increasing evidence implicates mitochondrial dysfunction and oxidative stress. To understand how mutations in alpha-synuclein contribute to the pathophysiology of PD, we undertook a proteomic analysis of transgenic mice overexpressing A30P alpha-synuclein to investigate which proteins are oxidized. We observed more than twofold selective increases in specific carbonyl levels of three metabolic proteins in brains of symptomatic A30P alpha-synuclein mice: carbonic anhydrase 2 (Car2), alpha-enolase (Eno1), and lactate dehydrogenase 2 (Ldh2). Analysis of the activities of these proteins demonstrates decreased functions of these oxidatively modified proteins in brains from the A30P compared to control mice. Our findings suggest that proteins associated with impaired energy metabolism and mitochondria are particularly prone to oxidative stress associated with A30P-mutant alpha-synuclein.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d850937b143884c0deabdc51aa67bfbeTest
https://doi.org/10.1016/j.nbd.2004.12.009Test

المؤلفون: Laura Mattavelli, Carlo Ferrarese, Maria Teresa Carrì, Simone Beretta, Arianna Casciati, Gessica Sala, Alberto Ferri, Chiara Ceresa

المساهمون: Beretta, S, Sala, G, Mattavelli, L, Ceresa, C, Casciati, A, Ferri, A, Carrì, M, Ferrarese, C

المصدر: Neurobiology of Disease, Vol 13, Iss 3, Pp 213-221 (2003)

مصطلحات موضوعية: animal diseases, Tetrazolium Salts, Fluorescent Antibody Technique, Mitochondrion, medicine.disease_cause, Neuroblastoma, Adenosine Triphosphate, Tumor Cells, Cultured, chemistry.chemical_classification, Cultured, Cell Death, biology, Blotting, Caspase 3, SOD1, Free Radical Scavengers, Tumor Cells, Mitochondria, Neurology, Caspases, Reactive Oxygen Specie, Western, Human, Programmed cell death, Blotting, Western, DNA Fragmentation, lcsh:RC321-571, Superoxide dismutase, medicine, Humans, Settore BIO/10, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Reactive oxygen species, L-Lactate Dehydrogenase, Superoxide Dismutase, Amyotrophic Lateral Sclerosis, Free Radical Scavenger, nutritional and metabolic diseases, n-Acetylcysteine, Caspase, Molecular biology, Acetylcysteine, nervous system diseases, Thiazoles, Cytosol, chemistry, Oxidative stress, Cell culture, Reactive Oxygen Species, Mutation, biology.protein, Mitochondrial function, Thiazole, Tetrazolium Salt, Amyotrophic Lateral Sclerosi

الوصف: We report that the expression of mutant G93A copper/zinc superoxide dismutase (SOD1), associated with familial amyotrophic lateral sclerosis, specifically causes a decrease in MTT reduction rate and ATP levels and an increase in both cytosolic and mitochondrial reactive oxygen species (ROS) production in human neuroblastoma SH-SY5Y cells compared to cells overexpressing wild-type SOD1 and untransfected cells. Exposure to N-acetylcysteine lowers ROS production and returns mitochondrial functional assays to control levels. No large aggregates of human SOD1 are detectable under basal growth conditions in any of the investigated cell lines. After proteasome activity inhibition, SOD1 aggregates can be detected exclusively in G93A-SOD1 cells, even though they do not per se enhance cell death compared to control cell lines. Our findings indicate that mitochondrial homeostasis is affected by mutant SOD1-generated ROS independently from the formation of aggregates and that this alteration is reversed by antioxidants.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::27dc7a73c71bed34f03df447e395057aTest
https://doi.org/10.1016/s0969-9961Test(03)00043-3