1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease.MPTP Poisoning: A condition caused by the neurotoxin MPTP which causes selective destruction of nigrostriatal dopaminergic neurons. Clinical features include irreversible parkinsonian signs including rigidity and bradykinesia (PARKINSON DISEASE, SECONDARY). MPTP toxicity is also used as an animal model for the study of PARKINSON DISEASE. (Adams et al., Principles of Neurology, 6th ed, p1072; Neurology 1986 Feb;36(2):250-8)Parkinsonian Disorders: A group of disorders which feature impaired motor control characterized by bradykinesia, MUSCLE RIGIDITY; TREMOR; and postural instability. Parkinsonian diseases are generally divided into primary parkinsonism (see PARKINSON DISEASE), secondary parkinsonism (see PARKINSON DISEASE, SECONDARY) and inherited forms. These conditions are associated with dysfunction of dopaminergic or closely related motor integration neuronal pathways in the BASAL GANGLIA.Parkinson Disease, Secondary: Conditions which feature clinical manifestations resembling primary Parkinson disease that are caused by a known or suspected condition. Examples include parkinsonism caused by vascular injury, drugs, trauma, toxin exposure, neoplasms, infections and degenerative or hereditary conditions. Clinical features may include bradykinesia, rigidity, parkinsonian gait, and masked facies. In general, tremor is less prominent in secondary parkinsonism than in the primary form. (From Joynt, Clinical Neurology, 1998, Ch38, pp39-42)1-Methyl-4-phenylpyridinium: An active neurotoxic metabolite of 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE. The compound reduces dopamine levels, inhibits the biosynthesis of catecholamines, depletes cardiac norepinephrine and inactivates tyrosine hydroxylase. These and other toxic effects lead to cessation of oxidative phosphorylation, ATP depletion, and cell death. The compound, which is related to PARAQUAT, has also been used as an herbicide.Substantia Nigra: The black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce DOPAMINE, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored MELANIN is a by-product of dopamine synthesis.Dopamine Agents: Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons.Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.Dopamine: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.Corpus Striatum: Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.Dopaminergic Neurons: Neurons whose primary neurotransmitter is DOPAMINE.Tyrosine 3-Monooxygenase: An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC 1.14.16.2.Striatonigral Degeneration: A sporadic neurodegenerative disease with onset in middle-age characterized clinically by Parkinsonian features (e.g., MUSCLE RIGIDITY; HYPOKINESIA; stooped posture) and HYPOTENSION. This condition is considered a clinical variant of MULTIPLE SYSTEM ATROPHY. Pathologic features include a prominent loss of neurons in the zona compacta of the SUBSTANTIA NIGRA and PUTAMEN. (From Adams et al., Principles of Neurology, 6th ed, p1075-6)Parkinson Disease: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4.3,4-Dihydroxyphenylacetic Acid: A deaminated metabolite of LEVODOPA.Levodopa: The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.Selegiline: A selective, irreversible inhibitor of Type B monoamine oxidase. It is used in newly diagnosed patients with Parkinson's disease. It may slow progression of the clinical disease and delay the requirement for levodopa therapy. It also may be given with levodopa upon onset of disability. (From AMA Drug Evaluations Annual, 1994, p385) The compound without isomeric designation is Deprenyl.Antiparkinson Agents: Agents used in the treatment of Parkinson's disease. The most commonly used drugs act on the dopaminergic system in the striatum and basal ganglia or are centrally acting muscarinic antagonists.Pyridinium CompoundsNeuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Homovanillic AcidGlobus Pallidus: The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus.Saimiri: A genus of the family CEBIDAE consisting of four species: S. boliviensis, S. orstedii (red-backed squirrel monkey), S. sciureus (common squirrel monkey), and S. ustus. They inhabit tropical rain forests in Central and South America. S. sciureus is used extensively in research studies.Neostriatum: The phylogenetically newer part of the CORPUS STRIATUM consisting of the CAUDATE NUCLEUS and PUTAMEN. It is often called simply the striatum.Mice, Inbred C57BLMazindol: Tricyclic anorexigenic agent unrelated to and less toxic than AMPHETAMINE, but with some similar side effects. It inhibits uptake of catecholamines and blocks the binding of cocaine to the dopamine uptake transporter.Monoamine Oxidase Inhibitors: A chemically heterogeneous group of drugs that have in common the ability to block oxidative deamination of naturally occurring monoamines. (From Gilman, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p414)Dyskinesias: Abnormal involuntary movements which primarily affect the extremities, trunk, or jaw that occur as a manifestation of an underlying disease process. Conditions which feature recurrent or persistent episodes of dyskinesia as a primary manifestation of disease may be referred to as dyskinesia syndromes (see MOVEMENT DISORDERS). Dyskinesias are also a relatively common manifestation of BASAL GANGLIA DISEASES.Sulfonium Compounds: Sulfur compounds in which the sulfur atom is attached to three organic radicals and an electronegative element or radical.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Dopamine Plasma Membrane Transport Proteins: Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of dopaminergic neurons. They remove DOPAMINE from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS and are the target of DOPAMINE UPTAKE INHIBITORS.Nerve Degeneration: Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.NortropanesCistanche: A plant genus of the family OROBANCHACEAE. Members contain phenylethanoid glycosides.Dyskinesia, Drug-Induced: Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)Motor Activity: The physical activity of a human or an animal as a behavioral phenomenon.Putamen: The largest and most lateral of the BASAL GANGLIA lying between the lateral medullary lamina of the GLOBUS PALLIDUS and the EXTERNAL CAPSULE. It is part of the neostriatum and forms part of the LENTIFORM NUCLEUS along with the GLOBUS PALLIDUS.Macaca fascicularis: A species of the genus MACACA which typically lives near the coast in tidal creeks and mangrove swamps primarily on the islands of the Malay peninsula.Clorgyline: An antidepressive agent and monoamine oxidase inhibitor related to PARGYLINE.Mesencephalon: The middle of the three primitive cerebral vesicles of the embryonic brain. Without further subdivision, midbrain develops into a short, constricted portion connecting the PONS and the DIENCEPHALON. Midbrain contains two major parts, the dorsal TECTUM MESENCEPHALI and the ventral TEGMENTUM MESENCEPHALI, housing components of auditory, visual, and other sensorimoter systems.Macaca mulatta: A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans.Herbicides: Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses (POACEAE), and woody plants. Some plants develop HERBICIDE RESISTANCE.Vesicular Monoamine Transport Proteins: A family of vesicular amine transporter proteins that catalyze the transport and storage of CATECHOLAMINES and indolamines into SECRETORY VESICLES.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Callithrix: A genus of the subfamily CALLITRICHINAE occurring in forests of Brazil and Bolivia and containing seventeen species.Vesicular Biogenic Amine Transport Proteins: Integral membrane proteins of the LIPID BILAYER of SECRETORY VESICLES that catalyze transport and storage of biogenic amine NEUROTRANSMITTERS such as ACETYLCHOLINE; SEROTONIN; MELATONIN; HISTAMINE; and CATECHOLAMINES. The transporters exchange vesicular protons for cytoplasmic neurotransmitters.Behavior, Animal: The observable response an animal makes to any situation.Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain.Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres.Dopamine Agonists: Drugs that bind to and activate dopamine receptors.Receptors, Dopamine D3: A subtype of dopamine D2 receptors that are highly expressed in the LIMBIC SYSTEM of the brain.NG-Nitroarginine Methyl Ester: A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.Conotoxins: Peptide neurotoxins from the marine fish-hunting snails of the genus CONUS. They contain 13 to 29 amino acids which are strongly basic and are highly cross-linked by disulfide bonds. There are three types of conotoxins, omega-, alpha-, and mu-. OMEGA-CONOTOXINS inhibit voltage-activated entry of calcium into the presynaptic membrane and therefore the release of ACETYLCHOLINE. Alpha-conotoxins inhibit the postsynaptic acetylcholine receptor. Mu-conotoxins prevent the generation of muscle action potentials. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed)Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Glial Cell Line-Derived Neurotrophic Factor: The founding member of the glial cell line-derived neurotrophic factor family. It was originally characterized as a NERVE GROWTH FACTOR promoting the survival of MIDBRAIN dopaminergic NEURONS, and it has been studied as a potential treatment for PARKINSON DISEASE.Rotenone: A botanical insecticide that is an inhibitor of mitochondrial electron transport.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Methyl Parathion: The methyl homolog of parathion. An effective, but highly toxic, organothiophosphate insecticide and cholinesterase inhibitor.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Autoradiography: The making of a radiograph of an object or tissue by recording on a photographic plate the radiation emitted by radioactive material within the object. (Dorland, 27th ed)Phenyl Ethers: Ethers that are linked to a benzene ring structure.Subthalamic Nucleus: Lens-shaped structure on the inner aspect of the INTERNAL CAPSULE. The SUBTHALAMIC NUCLEUS and pathways traversing this region are concerned with the integration of somatic motor function.alpha-Synuclein: A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.Receptors, Dopamine D2: A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D2-class receptor genes contain INTRONS, and the receptors inhibit ADENYLYL CYCLASES.Deep Brain Stimulation: Therapy for MOVEMENT DISORDERS, especially PARKINSON DISEASE, that applies electricity via stereotactic implantation of ELECTRODES in specific areas of the BRAIN such as the THALAMUS. The electrodes are attached to a neurostimulator placed subcutaneously.PC12 Cells: A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.Oxidopamine: A neurotransmitter analogue that depletes noradrenergic stores in nerve endings and induces a reduction of dopamine levels in the brain. Its mechanism of action is related to the production of cytolytic free-radicals.Nerve Tissue ProteinsOxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
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It appears that the N-methyl group of MPTP is required for neurotoxic activity. In animal experiments, only MPTP analogues that ... It is unlikely that the tetrahydropyridine byproducts that may be formed during the synthesis of PEPAP are neurotoxic in the ... Most structural changes, including replacing the N-methyl group with other substituents, abolished neurotoxicity. There is ... with an N-phenethyl group in place of the N-methyl substitution and an acetate ester rather than propionate. PEPAP is ...
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Replacing the α-methyl with a cyclopropyl dramatically reduces affinity for the noradrenaline transporter and 5-HT2A receptor ... This research was a continuation of earlier work from the same team which showed that replacing the α-methyl group of MDMA with ... MBDB Methyl-K (UWA-091) UWA-001 RTI-83 - another drug which selectively increases dopamine and serotonin levels without ... the only difference being the replacement of the α-methyl group with an α-cyclopropyl group. MDMA has been found in animal ...
PARP-1 accomplishes many of its roles through regulating poly(ADP-ribose) (PAR). PAR is a polymer that varies in length and can ... 4: 2240. Reynolds P, Cooper S, Lomax M, O'Neill P. 2015. Disruption of PARP1 function inhibits base excision repair of a sub- ... PARP-1 mediates parthanatos when it is over-activated in response to extreme genomic stress and synthesizes PAR which causes ... Once the PARP-1 protein recognizes the DNA damage, it catalyzes post-transcriptional modification of PAR. PAR will be formed ...
... (EC 1.13.12.11) is an enzyme with systematic name 1-methyl-4-phenyl-1,2,3,6- ... tetrahydropyridine:oxygen N-oxidoreductase. This enzyme catalyses the following chemical reaction 1-methyl-4-phenyl-1,2,3,6- ... tetrahydropyridine + O2 ⇌ {\displaystyle \rightleftharpoons } 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine N-oxide + methanol ... 2,3,6-tetrahydropyridine in mice". J. Pharmacol. Exp. Ther. 246: 1108-1115. PMID 3262153. Methylphenyltetrahydropyridine N- ...
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The initial velocity is defined as V 0 = d [ P ] / d t = k 2 [ ES ] {\displaystyle V_{0}=d[{{\ce {P}}}]/dt=k_{2}[{{\ce {ES ... In the simplest case of a single-substrate enzyme obeying Michaelis-Menten kinetics, the typical scheme E + S ⇌ k − 1 k 1 ES → ... K m app {\displaystyle K_{m}^{\text{app}}} , the substrate concentration that is needed to reach V max / 2 {\displaystyle V_{\ ... Cells in the central nervous system (astrocytes) include MAO-B that oxidizes MPTP to 1-methyl-4-phenylpyridinium (MPP+), which ...
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... methyl-4-phenyl-1,2,3,6-tetrahydropyridine), the precursor to MPP+, was found and linked to Parkinson's disease in the 1980s. ... 4, pages 125-129. See also: S. Hoogewerf and W.A. van Dorp (1886) "Sur quelques dérivés de l'isoquinoléine" (On some ... ISBN 978-0-85404-182-4. Brown, H.C., et al., in Baude, E.A. and Nachod, F.C., Determination of Organic Structures by Physical ... 1-Benzylisoquinoline is the structural backbone in naturally occurring alkaloids including papaverine. The isoquinoline ring in ...
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Structural analogs of desmethylprodine with different N-substituents than a methyl group on the piperidine have been ... 13 (4): 367-374. doi:10.1016/0376-8716(84)90004-8. PMID 6148225. Davis, G. C.; Williams, A. C.; Markey, S. P.; Ebert, M. H.; ... Desmethylprodine or 1-methyl-4-phenyl-4-propionoxypiperidine (MPPP, Ro 2-0718) is an opioid analgesic drug developed in the ... It was later found that his development of Parkinson's was due to a common impurity in the synthesis of MPPP called MPTP (1- ...
... phenyl)-, methyl ester MeSH D03.383.725.210 --- dimethindene MeSH D03.383.725.220 --- 2,2'-dipyridyl MeSH D03.383.725.227 --- ... phenyl)-, methyl ester MeSH D03.383.725.547.950 --- xanthinol niacinate MeSH D03.383.725.565 --- nicotinyl alcohol MeSH D03.383 ... phenyl)-1h-pyrazol-3-amine MeSH D03.383.129.539.200 --- epirizole MeSH D03.383.129.539.487 --- indazoles MeSH D03.383.129.539. ... 2,3,4,5-tetrahydro-8-chloro-3-methyl-5-phenyl-1h-3-benzazepin-7-ol MeSH D03.438.079.800 --- 2,3,4,5-tetrahydro-7,8-dihydroxy-1- ...
306 (1): 401-6. PMID 12721323. doi:10.1124/jpet.103.051912.. ,access-date=. захтева ,url=. (помоћ) ... Agonisti: 77-LH-28-1 • AC-42 • AC-260,584 • Aceklidin • Acetilholin • AF30 • AF150(S) • AF267B • AFDX-384 • Alvamelin • AQRA- ... Antagonisti: 3-Hinuklidinil Benzilat • 4-DAMP • Aklidinijum bromid • Anisodamin • Anisodin • Atropin • Atropin metonitrat • ... SIB-1553A je agonist nikotinskih acetilholinskih receptora koji je selektivan za receptore sa β4 podjedinicom. Administriranje ...
Agonisti: 77-LH-28-1 • AC-42 • AC-260,584 • Aceklidin • Acetilholin • AF30 • AF150(S) • AF267B • AFDX-384 • Alvamelin • AQRA- ... Antagonisti: 3-Hinuklidinil Benzilat • 4-DAMP • Aklidinijum bromid • Anisodamin • Anisodin • Atropin • Atropin metonitrat • ... 1-(-Benzoiletil)piridinijum • 2-(α-Naftoil)etiltrimetilamonijum • 3-Hloro-4-stilbazol • 4-(1-Naftilvinil)piridin • Acetilseko ... SIB-1553A je agonist nikotinskih acetilholinskih receptora koji je selektivan za receptore sa β4 podjedinicom. Administriranje ...
45 (2): 279-91. doi:10.1016/j.neuron.2005.01.003. PMID 15664179. Zuo Y, Lin A, Chang P, Gan WB (April 2005). "Development of ... 45 (3): 1051-67. doi:10.1016/j.nbd.2011.12.024. PMID 22198503. Janssen H, Bernhardt J, Collier JM, Sena ES, McElduff P, Attia J ... 77 (3): 696-711. doi:10.1111/j.1467-8624.2006.00898.x. PMID 16686796. Chugani HT, Behen ME, Muzik O, Juhász C, Nagy F, Chugani ... 70 (19 Pt 2): 1732-9. doi:10.1212/01.wnl.0000284603.85621.aa. PMID 18160675. Roe CM, Mintun MA, D'Angelo G, Xiong C, Grant EA, ...
... , also known as MAOB, is an enzyme that in humans is encoded by the MAOB gene. The protein encoded by this gene belongs to the flavin monoamine oxidase family. It is an enzyme located in the outer mitochondrial membrane. It catalyzes the oxidative deamination of biogenic and xenobiotic amines and plays an important role in the catabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. This protein preferentially degrades benzylamine and phenylethylamine. Like MAOA, it also degrades dopamine. Monoamine oxidase B has a hydrophobic bipartite elongated cavity that (for the "open" conformation) occupies a combined volume close to 700 Å3. hMAO-A has a single cavity that exhibits a rounder shape and is larger in volume than the "substrate cavity" of hMAO-B. The first cavity of hMAO-B has been termed the entrance cavity (290 Å3), the second substrate cavity or active site cavity (~390 Å3) - between both an isoleucine199 side-chain serves ...
... (phenethylphenylacetoxypiperidine) is an opioid analgesic that is an analog of pethidine (meperidine). It is related to the drug MPPP, with an N-phenethyl group in place of the N-methyl substitution and an acetate ester rather than propionate. PEPAP is approximately 6-7 times more potent than morphine in laboratory rats.[1] PEPAP presumably has similar effects to other opioids, producing analgesia, sedation and euphoria. Side effects can include itching, nausea and potentially serious respiratory depression which can be life-threatening. PEPAP has been found to be a potent CYP2D6 inhibitor, which makes it likely to cause adverse interactions with some other drugs, although the inhibitory potency of PEPAP is less than that of MPPP.[2] Both cocaine and methadone are also CYP2D6 inhibitors and could, in theory, potentiate the effect. It is unlikely that the tetrahydropyridine byproducts that may be formed during the synthesis of PEPAP are neurotoxic in the ...
Schneider, JS (July 2003). "The Subtype-Selective Nicotinic Acetylcholine Receptor Agonist SIB-1553A Improves Both Attention and Memory Components of a Spatial Working Memory Task in Chronic Low Dose 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Treated Monkeys". Journal of Pharmacology and Experimental Therapeutics 306 (1): 401-6. PMID 12721323. doi:10.1124/jpet.103.051912. Cite uses deprecated parameter ...
Schneider, JS (2003). „The Subtype-Selective Nicotinic Acetylcholine Receptor Agonist SIB-1553A Improves Both Attention and Memory Components of a Spatial Working Memory Task in Chronic Low Dose 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Treated Monkeys". Journal of Pharmacology and Experimental Therapeutics. 306 (1): 401-6. PMID 12721323. doi:10.1124/jpet.103.051912 ...
... (PNU-95,666) is a highly selective D2 receptor full agonist, the first of its kind to be discovered. It was developed for the treatment of Parkinson's disease and restless leg syndrome. While it has never been approved for medical use it is a highly valuable tool compound for basic research to identify neurobiological mechanisms that are based on a dopamine D2-linked (vs. D1, D3, D4, and D5-linked) mechanism of action. In 2004, Pfizer announced the end of their clinical development program for sumanirole, citing "recent studies that failed to sufficiently distinguish sumanirole from currently available therapies". Ropinirole Romero AG, et al. Synthesis of the selective D2 receptor agonist PNU-95666E from D-phenylalanine using a sequential oxidative cyclization strategy. Journal of Organic Chemistry. 1997; 62(19):6582. McCall RB, Lookingland KJ, Bédard PJ, Huff RM (September 2005). "Sumanirole, a highly dopamine D2-selective receptor agonist: in vitro and in vivo pharmacological ...
... (phenethylphenylacetoxypiperidine) is an opioid analgesic that is an analog of pethidine (meperidine). It is related to the drug MPPP, with an N-phenethyl group in place of the N-methyl substitution and an acetate ester rather than propionate. PEPAP is approximately 6-7 times more potent than morphine in laboratory rats.[1] PEPAP presumably has similar effects to other opioids, producing analgesia, sedation and euphoria. Side effects can include itching, nausea and potentially serious respiratory depression which can be life-threatening. PEPAP has been found to be a potent CYP2D6 inhibitor, which makes it likely to cause adverse interactions with some other drugs, although the inhibitory potency of PEPAP is less than that of MPPP.[2] Both cocaine and methadone are also CYP2D6 inhibitors and could, in theory, potentiate the effect. It is unlikely that the tetrahydropyridine byproducts that may be formed during the synthesis of PEPAP are neurotoxic in the ...
Oksidopamin (6-hidroksidopamin, 6-OHDA, 2,4,5-trihidroksifenetilamin) je neurotoksično sintetičko organsko jedinjenje koje se naučnim istraživanjima za selektivno uništavanje dopaminergičkih i noradrenergičkih neurona u mozgu. Smatra se 6-OHDA unose u neurone dopaminski i noradrenalinskih monoaminski transporteri.. Glavni oblik primene oksidopamina u istraživanjima je kao sredstvo za indukovanje Parkinsonizma kod laboratorijskih životinja kao što su miševi, pacovi i majmuni, koji se zatim koriste u razvoju i testiranju novih lekova i tretmana za Parkinsonovu bolest. Da bi se indukovolo ovo oboljenje kod životinja, oko 70% dopaminergičkih neurona u substantia nigra mozga mora biti uništeno. Osim oksidopamina može se koristiti MPTP. Ova agensa deluju putem formiranja reaktivnih oblika kiseonika kao što je radikal superoksida.[4]. ...
PTEN-induced putative kinase 1 (PINK1) is a mitochondrial serine/threonine-protein kinase encoded by the PINK1 gene. It is thought to protect cells from stress-induced mitochondrial dysfunction. PINK1 activity causes the parkin protein to bind to depolarized mitochondria to induce autophagy of those mitochondria. PINK1 is processed by healthy mitochondria and released to trigger neuron differentiation. Mutations in this gene cause one form of autosomal recessive early-onset Parkinson's disease. PINK1 is synthesized as a 63000 Da protein which is often cleaved by PARL, between the 103-Alanine and the 104-Phenylalanine residues, into a 53000 Da fragment. PINK1 contains an N-terminal mitochondrial localization sequence, a putative transmembrane sequence, a Ser/Thr kinase domain, and a C-terminal regulatory sequence. The protein has been found to localize to the outer membrane of mitochondria, but can also be found throughout the cytosol. Experiments suggest the Ser/Thr kinase domain faces ...
Parkinson's disease is the second most common neurodegenerative disorder[31] and manifests as bradykinesia, rigidity, resting tremor and posture instability. The crude prevalence rate of PD has been reported to range from 15 per 100,000 to 12,500 per 100,000, and the incidence of PD from 15 per 100,000 to 328 per 100,000, with the disease being less common in Asian countries. Parkinson's disease is a degenerative disorder of the central nervous system. It results from the death of dopamine-generating cells in the substantia nigra, a region of the midbrain; the cause of cell-death is unknown. The following paragraph is an excerpt from the Pathophysiology section of the article Parkinson's disease. The mechanism by which the brain cells in Parkinson's are lost may consist of an abnormal accumulation of the protein alpha-synuclein bound to ubiquitin in the damaged cells. The alpha-synuclein-ubiquitin complex cannot be directed to the proteasome. This protein accumulation forms proteinaceous ...
Parkinson's disease is the second most common neurodegenerative disorder[31] and manifests as bradykinesia, rigidity, resting tremor and posture instability. The crude prevalence rate of PD has been reported to range from 15 per 100,000 to 12,500 per 100,000, and the incidence of PD from 15 per 100,000 to 328 per 100,000, with the disease being less common in Asian countries. Parkinson's disease is a degenerative disorder of the central nervous system. It results from the death of dopamine-generating cells in the substantia nigra, a region of the midbrain; the cause of cell-death is unknown. The following paragraph is an excerpt from the Pathophysiology section of the article Parkinson's disease. The mechanism by which the brain cells in Parkinson's are lost may consist of an abnormal accumulation of the protein alpha-synuclein bound to ubiquitin in the damaged cells. The alpha-synuclein-ubiquitin complex cannot be directed to the proteasome. This protein accumulation forms proteinaceous ...
... (SS) also known as Dopamine-responsive dystonia (DRD), Segawa's disease, Segawa's dystonia and hereditary progressive dystonia with diurnal fluctuation, is a genetic movement disorder which usually manifests itself during early childhood at around ages 5-8 years (variable start age). Characteristic symptoms are increased muscle tone (dystonia, such as clubfoot) and Parkinsonian features, typically absent in the morning or after rest but worsening during the day and with exertion. Children with SS are often misdiagnosed as having cerebral palsy. The disorder responds well to treatment with levodopa. The disease typically starts in one limb, typically one leg. Progressive dystonia results in clubfoot and tiptoe walking. The symptoms can spread to all four limbs around age 18, after which progression slows and eventually symptoms reach a plateau. There can be regression in developmental milestones (both motor and mental skills) and failure to thrive in the absence of treatment. In ...
路易氏體失智症(英语:Dementia with Lewy bodies,縮寫為 DLB)是一種伴隨著行為(英语:Behavior change (individual))、認知及活動功能退化(英语:Parkinsonism)的失智症[1],患者的記憶力雖不見得在罹病初期就會衰退[2],但失智的情形還是會進行性疾病(英语:Progressive disease隨著時間逐漸惡化)[3],通常是當患者的認知功能退化到影響日常生活,之後接受檢查而確診[1][4]。。此症的主要特徵之一是動眼期睡眠行為障礙(英语:REM Behavioral ...
Ang karamdaman ni Parkinson o sakit ni Parkinson, kilala rin bilang paralysis agitans (paralisis na kumakalog), ay isang kronikong kapansanan ng sistemang nerbyos. Pinangalanan ito mula kay James Parkinson (1755-1824), isang manggagamot mula sa Londres, Inglatera. Ang isinaunang paglalarawan ng karamdaman ni Parkinson ay matatagpuan sa akdang An Essay on the Shaking Palsy ("Isang Sanaysay Hinggil sa Panghihinang Umaalog") sa ni James Parkinson na nalathala sa Londres noong 1817. Karaniwang nagaganap ang sakit na ito pagkaraan ng panahon ng gitnang buhay ng tao, na mas kadalasang nangyayari sa mga lalaki kaysa sa mga babae. Palihim ang pag-uumpisa ng karamdamang ito, at ang pagsulong ay kinatatangian ng pagkakaroon ng panghihina ng mga masel, paninigas at hindi mapagalaw na mga masel, at mga pangangatog. Nagkakaroon ang mukha ng hitsurang parang tuod, na tinatawag na maskara ni Parkinson, habang naninigas ang katawan. Nagkakaroon din ang may-sakit ng pestinasyon (mula sa Ingles na festination), ...
A tetrahydropyridine that is 1,2,3,6-tetrahydropyridine substituted by a methyl group at position 1 and a phenyl group at ... CHEBI:17963 - 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Main. ChEBI Ontology. Automatic Xrefs. Reactions. Pathways. Models ... 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine N-oxide (CHEBI:17472) has functional parent 1-methyl-4-phenyl-1,2,3,6- ... 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (CHEBI:17963) has role neurotoxin (CHEBI:50910) 1-methyl-4-phenyl-1,2,3,6- ...
Several individuals were identified who developed parkinsonism after self-injection of 1-methyl-4-phenyl-1,2,3,6- ... tetrahydropyridine (MPTP). These patients developed bradykinesia, rigidity, and tremor,... more ... 2C6-tetrahydropyridine (MPTP) cause Parkinson disease (PD)?) and Does 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) cause ... 6] MPP+ accumulates in mitochondria and interferes with the function of complex I of the respiratory chain. A chemical ...
Samuela Cataldi,1 Michela Codini,1 Stéphane Hunot,2 François-Pierre Légeron,2 Ivana Ferri,3 Paola Siccu,3 Angelo Sidoni,3 ... 1-8, 2017. View at Publisher · View at Google Scholar. *Samuela Cataldi, Cataldo Arcuri, Stéphane Hunot, Carmen Mecca, Michela ... 2Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Université Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle ... 3Institute of Pathologic Anatomy and Histology, University of Perugia, 06100 Perugia, Italy. 4Department of Clinical and ...
Reinhard JF Jr1, Daniels AJ, Viveros OH.. Author information. 1. Department of Medicinal Biochemistry, Wellcome Research ... Neurosci Lett. 1988 Aug 1;90(3):349-53.. Potentiation by reserpine and tetrabenazine of brain catecholamine depletions by MPTP ... These results are compatible with our hypothesis that sequestration of the toxic MPTP metabolite MPP+ (1-methyl-4- ... Administration to mice of the neurotoxicant MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) decreased striatal dopamine and ...
phenyl-. 3-. cyclohexen-. 1-. yl)methyl)pyridine 1,2,3,6-. tetrahydro-. 4-. phenyl-. 1-. ((3-. phenyl-. 3-. cyclohexen-. 1-. yl ... methyl-. 4-. phenyl-. 1,2,3,6-. tetrahydro-. 3-. pyridinol 1-. methyl-. 4-. phenyl-. 1,2,3,6-. (tetrahydropyridine)-. N-. oxide ... methyl)pyridine 1,2,3,6-. tetrahydro-. 4-. (p-. hydroxyphenyl)-. 1-. ((3-. (p-. hydroxyphenyl)-. 3-. cyclohexen-. 1-. yl)methyl ... 3-. trifluoro-. N-. methyl-. 4-. phenyl-. 1,2,3,6-. tetrahydropyridine 4-. (4-. methoxy-. 1,2,5-. thiadiazol-. 3-. yl)-. 1- ...
... and N-methyl-β-carbolinium-βC+-) by MAO and heme peroxidases and the rate of inactivation (i.e., N-demethylation, aromatic ... MAO catalyzed the oxidation of MPTP to 1-methyl-4-phenyl-2,3-dihydropyridinium cation (MPDP+), whereas heme peroxidases ... Metabolic enzymes are involved in the activation/deactivation of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyiridine (MPTP) ... and of 2-methyltetrahydro-β-carboline to 2-methyl-3,4-dihydro-β-carbolinium cation (2-Me-3,4-DHβC+). These substances were ...
3,6-tetrahydropyridine (MPTP). The concentration-dependency of H2 showed that H2 as low as 0.08 ppm had almost the same effect ... 4-HNE), a marker of lipid peroxidation were significantly decreased in the nigro-striatal dopaminergic pathway in mice drinking ... reduced the loss of dopaminergic neurons in PD model mice using both acute and chronic administration of 1-methyl-4-phenyl-1,2, ... as saturated H2 water (1.5 ppm). MPTP-induced accumulation of cellular 8-oxoguanine (8-oxoG), a marker of DNA damage, and 4- ...
2,3,6-tetrahydropyridine (MPTP) and L-DOPA treatment. The common marmoset (Callithrix jacchus) shows parkinsonian motor d … ... of patients with Parkinsons disease chronically treated with L-DOPA and also occur in several nonhuman primate species after 1 ... phenyl-1,2,3,6-tetrahydropyridine-treated common marmoset (Callithrix Jacchus) Mov Disord. 1995 Nov;10(6):731-40. doi: 10.1002/ ... R K Pearce 1 , M Jackson, L Smith, P Jenner, C D Marsden ... Chronic L-DOPA administration induces dyskinesias in the 1- ...
2.Department of Medicine, Infectious Diseases DivisionIcahn School of Medicine at Mount SinaiNew YorkUSA ... Dickens AM, Yoo SW, Chin AC, Xu J, Johnson TP, Trout AL, Hauser KF, Haughey NJ (2017) Chronic low-level expression of HIV-1 tat ... Lu SM, Tremblay ME, King IL, Qi J, Reynolds HM, Marker DF, Varrone JJ, Majewska AK, Dewhurst S, Gelbard HA (2011) HIV-1 tat- ... Zauli G, Secchiero P, Rodella L, Gibellini D, Mirandola P, Mazzoni M, Milani D, Dowd DR, Capitani S, Vitale M (2000) HIV-1 tat- ...
Cagen SZ, Janoff AS, Bus JS, Gibson JE 1976 Effect of paraquat (methyl viologen) on liver function in mice J Pharmacol Exp Ther ... di methyl-4,4′-bipyridium dichloride (paraquat, PQ) (Catalog #36541 Sigma-St. Louis, MO) was dissolved in sterile saline to a ... di methyl-4,4′-bipyridium dichloride (paraquat, PQ). PQ is a commonly used non-selective herbicide that has been ... 1: p≤0.05, C57BL/6J PQ+no heat vs C57BL/6J PQ+Heat. 2: p≤0.05, C57BL/6J PQ+no heat vs C57BL/6J saline+no heat. 3: p≤0.05, C57BL ...
3. Variation in formation rates of PTP (A), MPDP+ (B), MPTP N-oxide (C), and MPP+ (D) from MPTP by liver and brain microsomes ... 4. Effects of chemical inhibitors on the formation rates of PTP (A), MPDP+ (B), MPTP N-oxide (C), and MPP+ (D) from MPTP in ... 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. P450. cytochrome P450. PCR. polymerase chain reaction. PTP. 4-phenyl-1,2,3,6- ... tetrahydropyridine. RT. reverse transcription. *Copyright © 2015 by The American Society for Pharmacology and Experimental ...
Methyl4Phenyl1,2,3,6Tetrahydropyridine in Mouse Brain, Journal of Neurochemistry" on DeepDyve, the largest online rental ... Energy‐dependent uptake of N‐methyl4‐phenylpyridinium, the neurotoxic metabolite of 1methyl4phenyl1,2,3,6‐ ... Methyl4Phenyl1,2,3,6Tetrahydropyridine in Mouse Brain. Chan, Piu; DeLanney, Louis E.; Irwin, Ian; Langston, J. William; ... Tetrahydropyridine in Mouse Brain. Rapid ATP Loss Caused by 1Methyl4Phenyl1,2,3,6Tetrahydropyridine in Mouse Brain Chan, ...
Addition of 10 microM 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the culture medium for 4 to 7 days resulted in ... Selective decrease of immunoreactive tyrosine hydroxylase in nigrostriatum of adult male rats after N-methyl-4-phenyl-1,2,3,6- ... tetrahydropyridine treatment. *Dr. Linda L. Vacca-Galloway, Ryoichi Ikeda, Shirley Y. Coleman ... 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine destroys dopamine neurons in explants of rat embryo mesencephalon.. @article{ ...
SAM is the endogenous methyl donor for DA [17]. And it caused the depletion of striatal DA [18] and the loss of TH and DA cells ... phenyl-1,2,3,6-tetrahydropyridine (MPTP) Administration," Neuroscience, Vol. 169, No. 3, 2010, pp. 1085-1093. doi:10.1016/j. ... Figure 2. The effects of postnatal doses of 0 (PBS), 10, 20 and 30 mg/kg of MPTP on midbrain DA, DOPAC, HVA and 3-MT in C57BL/ ... Table 2. The effects of postnatal-MPTP of 10, 20 and 30 mg/kg or PBS on midbrain DA, DOPAC, 3-MT and HVA in offspring exposed ...
A late (days 6-11) increase in striatal dopamine oxidative metabolism, ascorbic acid oxidative status, and catabolites of high- ... The Neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induces apoptosis in mouse nigrostriatal glia. Relevance to nigral ... Swiss mice were given 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 25 mg/kg/day, for 5 consecutive days and killed at ... Decreases in striatal tyrosine hydroxylase activity and levels of dopamine and its metabolites were observed 1 day after MPTP ...
In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice, GM-CSF given prior to MPTP protected nigral ... In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice, GM-CSF given prior to MPTP protected nigral ... In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice, GM-CSF given prior to MPTP protected nigral ... In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice, GM-CSF given prior to MPTP protected nigral ...
To adequately quantify TH-positive neurons, we used the nuclear counterstain methyl green (Vector Laboratories) and the ... 4 A and B), but does so quite effectively in the presence of glia (Fig. 4 C and D), we argue that the neurotoxicity of MPTP/MPP ... 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine;. MPP+,. 1-methyl-4-phenylpyridinium;. SNpc,. substantia nigra pars compacta;. CGN ... 3,4-dihydroxyphenylacetic acid;. HVA,. homovanilic acid;. MAPK,. mitogenactivated protein kinase;. TH,. tyrosine hydroxylase;. ...
... an update on the acute and chronic manifestations of methyl mercury poisoning. J Neurol Sci 262:131-144PubMedCrossRefGoogle ... 3.Department of Radiology and Nuclear MedicineGhent UniversityGhentBelgium. *4.Netherlands Organization for Applied Scientific ... 1.Department of Nuclear Medicine and Molecular ImagingUniversity Medical Center Groningen, University of GroningenGroningenThe ... 2.Department of Nuclear Medicine and Molecular ImagingUniversity of Groningen, University Medical Center GroningenGroningenThe ...
Involvement of the Fc{gamma} Receptor in a Chronic N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Mouse Model of Dopaminergic ... Activated microglia are critical for N-methyl-d-aspartate-induced neurodegeneration in slice cultures (28). β-Amyloid in ... 4. TLR4 is necessary for LPS-induced neuronal injury in vitro. Mixed CNS cultures prepared from BALB/cJ and lpsd mouse ... 3C).. Microglia bind Alexa-tagged LPS in vitro, whereas oligodendrocytes and astrocytes do not (16). Thus, we next asked ...
PREFACE xi. ACKNOWLEDGMENTS xiii. INTRODUCTION 1. SPECIFIC METHODS FOR THE DESTRUCTION OF HAZARDOUS CHEMICALS IN THE LABORATORY 17. Acetonitrile 19. Acid Halides and Anhydrides 23. Aflatoxins 29. Alkali and Alkaline Earth Metals 37. Alkali Metal Alkoxides 41. Anatoxin-A 43. Aromatic Amines 47. Arsenic 57. Azides 61. Azo and Azoxy Compounds and Tetrazenes 69. Boron Trifluoride and Inorganic Fluorides 77. Botulinum Toxins 81. Brevetoxins 85. Butyllithium 89. Calcium Carbide 93. Carbamic Acid Esters 95. Carbofuran 99. Chloromethylsilanes and Silicon Tetrachloride 101. N-Chlorosuccinimide and Chloramine-T 103. Chlorosulfonic Acid 105. Chromium(VI) 107. Citrinin 113. Complex Metal Hydrides 121. Cyanides and Cyanogen Bromide 129. Cylindrospermopsin 137. Diisopropyl Fluorophosphate 141. Dimethyl Sulfate and Related Compounds 151. Dyes and Biological Stains 163. Ethidium Bromide 201. Haloethers 211. Halogenated Compounds 217. Halogens 229. Heavy Metals 233. Hexamethylphosphoramide 241. Hydrazines ...
Hepad 1 and 2 remarkably alleviated the enhanced expression of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin ... Therefore, our results suggest that Hepad 1 and 2 are useful for treating PD and other disorders associated with neuro- ... The present study demonstrated that the herbal medicines Hepad 1 and 2 protected against 1-methyl-4-phenyl-1,2,3,6- ... tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity in C57BL/6 mice and SH-SY5Y cells. ...
2B). The normalized peak time and amplitude were calculated for each neuron for the early (Fig. 2C) and late (Fig. 2D) ... 2A), where GPe neurons tended to fire 3.5 ± 0.13 ms (mean ± SEM) after the stimulus, and GPi neurons tended to fire at a ... 2E), indicating a decay of the time-locked response over time. Of the neurons that showed an evolving time-locked response to ... Figure 2. Time-locked response changes during stimulation. A, Population PSTH of all GPe (blue) and GPi (red) neurons during ...
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a prodrug to the neurotoxin MPP+, which causes permanent symptoms of ... 1 (3): 249-254. doi:10.1016/0165-1781(79)90006-4. CS1 maint: Multiple names: authors list (link) "Success reported using fetal ... 12 (6): 885-893. doi:10.1021/jo01170a021. Vinken, P. J.; Bruyn, G. W. (1994). Intoxications of the Nervous System. Elsevier ... "1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine". ChemIDplus. Langston, J. W. (2002). "Chapter 30 The Impact of MPTP on ...
Methyl-4-phenyl-1,2,3,6-tetrahydropyridine. MS. Multiple sclerosis. NFTs. Neurofibrillary tangles ... 2.. Olesen J, Gustavsson A, Svensson M et al (2012) The economic cost of brain disorders in Europe. Eur J Neurol 19:155-162 ... 1.. Hung CW, Chen YC, Hsieh WL, Chiou SH, Kao CL (2010) Ageing and neurodegenerative diseases. Ageing Res Rev 9(Suppl 1):S36- ... 1.Dipartimento di Scienze per la Qualità della VitaAlma Mater Studiorum, Università di BolognaRiminiItaly ...
dynamin related-protein 1. HD. Huntingtons disease. Hsp. heat shock protein. htt. huntingtin. mhtt. mutant htt. LRRK2. leucine ... 3-NP. 3-nitropropionic acid. OMM. outer mitochondrial membrane. OPA1. optic atrophy 1. PD. Parkinsons disease. PGC-1α. ... 5-aminoimidazole-4-carboxamide ribonucleoside. ALS. amyotrophic lateral sclerosis. AMPK. AMP-activated protein kinase. APP. ... 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. mtDNA. mitochondrial DNA. NRF. nuclear respiratory factor. ...
  • Activation of microglia, bone marrow-derived macrophage-like cells that function as the resident immune defense system of the brain ( 1 ), is a characteristic feature of most neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, multiple sclerosis, AIDS dementia complex, and amyotrophic lateral sclerosis as well as ischemia and posttraumatic brain injury ( 2 - 4 ). (pnas.org)
  • These inclusions, subsequently termed Lewy bodies, were distinct both in their morphology and location from inclusions found in other neurodegenerative diseases, e.g. extracellular amyloid plaques of Alzheimer's and intranuclear inclusions of Huntington's disease [ 2 ]. (biochemj.org)
  • Substantial evidence now demonstrates that microglia-mediated inflammatory processes play an important role in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease (PD), 3 Alzheimer's disease, multiple sclerosis, and the AIDS dementia complex ( 1 , 2 , 3 ). (jimmunol.org)
  • Given that IL-1β release is a well-accepted marker for inflammatory microglial activation, plus findings that IL-1β is overexpressed both in AD and PD brain, it is worth exploring whether targeting GSTO1 would be an effective way to inhibit inflammation, and possibly prevent neurodegeneration in Alzheimer's, conclude the authors. (alzforum.org)
  • The donating investigator reported that resulting chimeric animals were backcrossed to C57BL/6 (see SNP note below) for ten generations before being made homozygous. (jax.org)
  • While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 2 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. (jax.org)
  • In 2013, the same SNP panel analysis showed 4 of 5 markers that determine C57BL/6J from C57BL/6N were segregating. (jax.org)
  • Taken together, our results show that TGF-β1 exerted potent anti-inflammatory and neuroprotective properties, either through the prevention of the direct activation of microglia by LPS, or indirectly through the inhibition of reactive microgliosis elicited by 1-methyl-4-phenylpyridinium. (jimmunol.org)
  • The peak magnitudes of α-syn inclusion formation, MHC-II expression, and reactive microglial morphology were all observed in the SN 2 months following injection and 3 months prior to nigral dopamine neuron loss. (biomedcentral.com)
  • Although activation of microglia serves an important protective function in immune surveillance by removing foreign microorganisms ( 4 ), overactivation of microglia followed by overproduction of proinflammatory factors has been shown to result in neuronal death in the brain ( 5 , 6 ). (jimmunol.org)
  • The neuroprotective effect of minocycline is associated with marked reductions in inducible NO synthase (iNOS) and caspase 1 expression. (pnas.org)
  • Hepad 1 and 2 remarkably alleviated the enhanced expression of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2, macrophage-1, and phosphorylated iκB-α) and apoptotic signals (Bcl-2-associated X protein, caspase-3, and poly [ADP-ribose] polymerase-1). (mdpi.com)
  • Diadenosine Tetraphosphate Protects Against Injuries Induced by Ischemia and 6-hydroxydopamine in Rat Brain The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. (jove.com)
  • Brain Research Reviews, 27, 1-39. (scirp.org)
  • Identification of differentiation-associated brain-specific phosphate transporter as a second vesicular glutamate transporter (VGLUT 2). (mpg.de)
  • The leukemic oncogene tal-2 is expressed in the developing mouse brain. (mpg.de)
  • Two types of TH mRNA corresponding to type 1 and type 2 were detected in adrenal gland and brain of two species of primate. (nii.ac.jp)
  • The aim of this study was to characterize effects in the brain of 6-month-old rats treated neonatally (postnatal days 910) with the glutamatergic BMAA. (diva-portal.org)
  • PQ is a commonly used non-selective herbicide that has been epidemiological linked to Parkinson's disease [ 3, 4 ]. (iospress.com)
  • The signs and symptoms of Parkinson's disease can be treated with drugs that increase or enhance dopamine function, but these drugs fail to alter disease progression and most produce undesirable side effects, like motor fluctuations and dyskinesias ( 2 ). (pnas.org)
  • In that North American multicenter Phase 2 trial, 80 people newly diagnosed with Parkinson's disease received one of three daily doses (300, 600, or 1200 mg) of CoQ10 or a placebo. (alzforum.org)
  • Approximately a century ago, Friedrich Lewy made a key discovery towards the understanding of Parkinson's disease (PD) by identifying and describing large cytoplasmic proteinacious inclusions in brains of patients who had died with the disease [ 1 ]. (biochemj.org)
  • In this study, using the well-established LPS and the 1-methyl-4-phenylpyridinium-mediated models of Parkinson's disease, we demonstrate that TGF-β1 exerts significant neuroprotection in both models via its anti-inflammatory properties. (jimmunol.org)
  • 1. A method of treating a patient with Parkinson's disease or Parkinsonian disorders comprising administering PDGF-BB in vivo directly to the central nervous system of said patient, wherein the PDGF-BB is administered in an amount of between 0.5 ng/kg/day to 500 ng/kg/day. (google.com)
  • These observations suggest that bvPLA 2 -CD206-PGE 2 -EP2 signaling promotes immune tolerance through Treg differentiation and contributes to the prevention of various neurodegenerative diseases, including Parkinson's disease. (jimmunol.org)
  • 2. A. Moran, I. Bar-Gad / Journal of Neuroscience Methods 186 (2010) 116-129 117 ern multi-electrode equipment (Bartho et al. (slideshare.net)
  • Airas L, Paavilainen T, Marttila RJ, Rinne J (2008) Methanol intoxication-induced nigrostriatal dysfunction detected using 6-[ 18 F]fluoro-L-dopa PET. (springer.com)
  • This olfactory dysfunction can occur up to 10 years before the onset of motor symptoms and the clinical diagnosis of PD 3 , 4 . (nature.com)
  • 2. Characterization of a novel mitochondria-to-nucleus stress signaling in cells subjected to mitochondrial specific genetic, and or, metabolic stress, which operates through altered [Ca2+]c, and the role of mitochondrial stress signaling in tumor progression and metastasis. (upenn.edu)
  • 4. Role of mitochondrial stress signaling in Embryonic Stem Cell function/differentiation, and mammalian mitochondrial transcription under chemical and oxidative stress in ES cells. (upenn.edu)
  • AP4A suppressed terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) induced by hypoxia/reperfusion in primary cortical cultures, and reduced both ischemia-induced translocation of mitochondrial cytochrome c and the increase in cytoplasmic caspase-3 activity in vivo. (jove.com)
  • After discovery of nitric oxide as a biological mediator many researchers have focused on the importance of nitric oxide in the physiology of the nervous system [ 1 - 3 ]. (intechopen.com)
  • It is related to the drug MPPP , with an N -phenethyl group in place of the N - methyl substitution and an acetate ester rather than propionate . (wikipedia.org)
  • There is evidence that the clandestine manufacturers who produced MPPP in the 1970s, including the tainted batch, went on to produce PEPAP [4] in an attempt to avoid using watched precursors or drug intermediates that were illegal. (wikipedia.org)
  • Therefore, our results suggest that Hepad 1 and 2 are useful for treating PD and other disorders associated with neuro-inflammatory, neuro-apoptotic, and neuro-oxidative damage. (mdpi.com)
  • While PGE 2 is a well established modulator of inflammatory responses in many different contexts, and it affects the progression and outcome of a wide range of disease processes, its in vivo cell- and receptor-specific mechanisms of inflammatory action are incompletely understood. (jneurosci.org)
  • In innate and adaptive immune responses, PGE 2 can elicit both immunosuppressive as well as proinflammatory effects, suggesting that the specificity of the PGE 2 inflammatory response depends not only on the type of stimulus, but on the specific EP receptors and immune cell types that are activated. (jneurosci.org)
  • 3. Regulation of cytochrome oxidase gene expression, and modulation of enzyme assembly/activity under chemical and oxidative stress conditions. (upenn.edu)
  • Supersensitivity of the D1 ( 5 ) and D2 ( 6 , 7 ) dopamine receptors is thought to be among the molecular mechanisms underlying LID. (sciencemag.org)
  • Molecular cloning and functional characterization of human vesicular glutamate transporter 3. (mpg.de)
  • Apoptosis was tested by terminal deoxynucleotidyl transferase-mediated 2′-deoxy-uridine-5′-triphosphate nick end labelling (TUNEL) technique, flow cytometry and fluorescence microscopy. (deepdyve.com)
  • 2. A method for inducing the in situ proliferation or differentiation of neural stem cells or neural progenitor cells located in a neural tissue of a human, the method comprising administering an amount of PDGF-BB of between 0.5 ng/kg/day to 500 ng/kg/day, to the neural tissue to induce the proliferation or differentiation of the neural stem cells or neural progenitor cells. (google.com)
  • N -methylpyridinium-MPP + and MPDP + - and N -methyl- β -carbolinium- β C + -) by MAO and heme peroxidases and the rate of inactivation (i.e. (hindawi.com)
  • The 5'-flanking of the genes of human TH, DBH and PNMT contain … More possible transcription regulatory elements such as cyclic AMP responsive element (CRE) (TH, DBH, PNMT), glucocorticoid responsive element (GRE) (DBH, PNMT), and Sp 1 (TH, PNMT) binding site. (nii.ac.jp)
  • Blocking of FKHR/FKHRL-1 dephosphorylation after seizures improved hippocampal neuronal survival in vivo, and Bim antisense oligonucleotides were neuroprotective against seizures in vitro. (jci.org)
  • Here, we investigated the cell-specific in vivo function of PGE 2 signaling through its E-prostanoid 2 (EP2) receptor in murine innate immune responses systemically and in the CNS. (jneurosci.org)
  • In vivo absorption and metabolism of leptosperin and methyl syringate, abundantly present in manuka honey. (semanticscholar.org)
  • 1. Mechanisms of dual targeting of cytochrome P450 and related proteins to ER and mitochondria and mechanisms of activation of the chimeric N-terminal signal by cAMP and other physiological factors. (upenn.edu)
  • Sections of SNc showed some terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL)-positive cells. (uniss.it)
  • Publications] Kojima,K.: 'Microbore HPLC for biological samples: catecholamines,peptides and proteins.In: PROGRESS IN HPLC,Vol. 4' M.Yoshioka,S.Parvez,H.Parvez (Eds. (nii.ac.jp)
  • Blots of striatal homogenates probed with phosphorylation-state specific antibodies, demonstrated significant changes in activated forms ERK 1/2, JNK, MEK1/2, p70 S6 kinase, CREB, and Stat3 as early as one hour after insult, with the largest activation at time points (6 and 12h) preceding the peak induction of GFAP (48h post treatment). (cdc.gov)
  • A late (days 6-11) increase in striatal dopamine oxidative metabolism, ascorbic acid oxidative status, and catabolites of high-energy phosphates were observed concomitant with nigral neuron and nigrostriatal glial cell apoptotic death, as revealed by TUNEL, acridine orange, and Hoechst staining, and transmission electron microscopy. (uniss.it)
  • We show that in the CNS, specific activation of innate immunity through a Toll-like receptor 4 (TLR4)-dependent pathway leads to neurodegeneration. (pnas.org)