CAS: 23007-85-4; Mptp (Hydrochloride)

相似化合物

28289-54-5 186347-72-8 38025-45-5

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参考文献:Preferential Extracellular Generation Of The Active Parkinsonian Toxin Mpp+by Transporter-Independent Export Of The Intermediate Mpdp+
标题:Preferential Extracellular Generation Of The Active Parkinsonian Toxin Mpp+by Transporter-Independent Export Of The Intermediate Mpdp+
摘要:Aims: 1-Methyl-4-Phenyl-Tetrahydropyridine (Mptp) Is Among The Most Widely Used Neurotoxins For Inducing Experimental Parkinsonism. Mptp Causes Parkinsonian Symptoms In Mice,Primates,And Humans By Killing A Subpopulation Of Dopaminergic Neurons. Extrapolations Of Data Obtained Using Mptp-Based Parkinsonism Models To Human Disease Are Common; However,The Precise Mechanism By Which Mptp Is Converted Into Its Active Neurotoxic Metabolite,1-Methyl-4-Phenyl-Pyridinium (Mpp+),Has Not Been Fully Elucidated. In This Study,We Aimed To Address Two Unanswered Questions Related To Mptp Toxicology: (1) Why Are Mptp-Converting Astrocytes Largely Spared From Toxicity (2) How Does Mpp+ Reach The Extracellular Space Results: In Mptp-Treated Astrocytes,We Discovered That The Membrane-Impermeable Mpp+,Which Is Generally Assumed To Be Formed Inside Astrocytes,Is Almost Exclusively Detected Outside Of These Cells. Instead Of A Transporter-Mediated Export,We Found That The Intermediate,1-Methyl-4-Phenyl-2,3-Dihydropyridinium (Mpdp+),And/or Its Uncharged Conjugate Base Passively Diffused Across Cell Membranes And That Mpp+ Was Formed Predominately By The Extracellular Oxidation Of Mpdp+ Into Mpp+. This Nonenzymatic Extracellular Conversion Of Mpdp+ Was Promoted By O-2,A More Alkaline Ph,And Dopamine Autoxidation Products. Innovation And Conclusion: Our Data Indicate That Mptp Metabolism Is Compartmentalized Between Intracellular And Extracellular Environments,Explain The Absence Of Toxicity In Mptp-Converting Astrocytes,And Provide A Rationale For The Preferential Formation Of Mpp+ In The Extracellular Space. The Mechanism Of Transporter-Independent Extracellular Mpp+ Formation Described Here Indicates That Extracellular Genesis Of Mpp+ From Mpdp Is A Necessary Prerequisite For The Selective Uptake Of This Toxin By Catecholaminergic Neurons.
Doi:10.1089/ars.2015.6297

专利信息

专利号:US-11472777-B2
优先权日:2015-09-14
标题:Piperazine and piperidine derivatives, their synthesis and use thereof in inhibiting VDAC oligomerization, apoptosis and mitochondria dysfunction
发明人：SHOSHAN-BARMATZ VARDA; LEV GRUZMAN ARIE
权利人:NAT INST BIOTECHNOLOGY NEGEV LTD
摘要:Provided herein piperazine and piperidine derivatives, their synthesis and use thereof in inhibiting VDAC oligomerization, apoptosis and mitochondria dysfunction. Also provided methods of treatment of diseases associated with said processes, e.g. Alzheimer's and Parkinson's diseases.

专利号:US-7588757-B2
优先权日:2001-03-14
标题 :Methods of treating Parkinson's disease using recombinant adeno-associated virus virions
发明人：OZAWA KEIYA; FUJIMOTO KEN-ICHI; MURAMATSU SHIN-ICHI; IKEGUCHI KUNIHIKO; NAKANO IMAHARU
权利人:GENZYME CORP
摘要:Methods for treating Parkinson's disease (PD) are provided. Recombinant adeno-associated virus (rAAV) virions are used to deliver genes encoding dopamine-synthesizing enzymes to the central nervous system of a primate. Once delivered, the genes are expressed, which then results in dopamine synthesis and amelioration in the clinical signs and symptoms of PD. The methods of the present invention can be used to deliver the three central dopamine synthesizing enzymes: tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and guanosine triphosphate cyclohydrolase I thereby enhancing dopamine biosynthesis and providing for enhanced therapeutic efficacy.

专利号:US-10342851-B2
优先权日:2012-02-29
标 题 :Use of engrailed proteins for increasing dopamine synthesis by dopaminergic neurons

专利号:RU-2134264-C1
优先权日:1994-04-19
标题 :Derivatives of tropan-2-aldoxime, method of their synthesis, pharmaceutical composition and substances for drug production on said, method of treatment of patients with disorder or disease

专利号:US-2015057231-A1
优先权日:2012-02-29
标题 :Use of Engrailed Proteins for Increasing Dopamine Synthesis by Dopaminergic Neurons

专利号:US-2018271937-A1
优先权日:2012-02-29
标题:Use of Engrailed Proteins for Increasing Dopamine Synthesis by Dopaminergic Neurons