Home > Publications Database > Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson's disease. > print

001     139516
005     20240321220631.0
024 7 _ |a 10.1126/science.aam9080
|2 doi
024 7 _ |a pmid:28882997
|2 pmid
024 7 _ |a pmc:PMC6021018
|2 pmc
024 7 _ |a 0036-8075
|2 ISSN
024 7 _ |a 1095-9203
|2 ISSN
024 7 _ |a 1947-8062
|2 ISSN
024 7 _ |a altmetric:24916218
|2 altmetric
037 _ _ |a DZNE-2020-05838
041 _ _ |a English
082 _ _ |a 320
100 1 _ |a Burbulla, Lena F
|0 P:(DE-HGF)0
|b 0
245 _ _ |a Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson's disease.
260 _ _ |a Washington, DC
|c 2017
|b Assoc.60841
264 _ 1 |3 online
|2 Crossref
|b American Association for the Advancement of Science (AAAS)
|c 2017-09-07
264 _ 1 |3 print
|2 Crossref
|b American Association for the Advancement of Science (AAAS)
|c 2017-09-22
336 7 _ |a article
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336 7 _ |a Output Types/Journal article
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336 7 _ |a Journal Article
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|s 1589210613_516
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336 7 _ |a ARTICLE
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336 7 _ |a JOURNAL_ARTICLE
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336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a Mitochondrial and lysosomal dysfunction have been implicated in substantia nigra dopaminergic neurodegeneration in Parkinson's disease (PD), but how these pathways are linked in human neurons remains unclear. Here we studied dopaminergic neurons derived from patients with idiopathic and familial PD. We identified a time-dependent pathological cascade beginning with mitochondrial oxidant stress leading to oxidized dopamine accumulation and ultimately resulting in reduced glucocerebrosidase enzymatic activity, lysosomal dysfunction, and α-synuclein accumulation. This toxic cascade was observed in human, but not in mouse, PD neurons at least in part because of species-specific differences in dopamine metabolism. Increasing dopamine synthesis or α-synuclein amounts in mouse midbrain neurons recapitulated pathological phenotypes observed in human neurons. Thus, dopamine oxidation represents an important link between mitochondrial and lysosomal dysfunction in PD pathogenesis.
536 _ _ |a 345 - Population Studies and Genetics (POF3-345)
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536 _ _ |a 344 - Clinical and Health Care Research (POF3-344)
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542 _ _ |i 2017-09-22
|2 Crossref
|u http://www.sciencemag.org/about/science-licenses-journal-article-reuse
588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a Antioxidants
|2 NLM Chemicals
650 _ 7 |a Calcineurin Inhibitors
|2 NLM Chemicals
650 _ 7 |a Melanins
|2 NLM Chemicals
650 _ 7 |a alpha-Synuclein
|2 NLM Chemicals
650 _ 7 |a neuromelanin
|2 NLM Chemicals
650 _ 7 |a PARK7 protein, human
|0 EC 3.1.2.-
|2 NLM Chemicals
650 _ 7 |a Protein Deglycase DJ-1
|0 EC 3.1.2.-
|2 NLM Chemicals
650 _ 7 |a Glucosylceramidase
|0 EC 3.2.1.45
|2 NLM Chemicals
650 _ 7 |a Dopamine
|0 VTD58H1Z2X
|2 NLM Chemicals
650 _ 7 |a Tacrolimus
|0 WM0HAQ4WNM
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Antioxidants: pharmacology
|2 MeSH
650 _ 2 |a Calcineurin Inhibitors: pharmacology
|2 MeSH
650 _ 2 |a Cell Line
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Dopamine: metabolism
|2 MeSH
650 _ 2 |a Dopaminergic Neurons: metabolism
|2 MeSH
650 _ 2 |a Glucosylceramidase: deficiency
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Lysosomes: metabolism
|2 MeSH
650 _ 2 |a Melanins: metabolism
|2 MeSH
650 _ 2 |a Mesencephalon: enzymology
|2 MeSH
650 _ 2 |a Mesencephalon: metabolism
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mice, Knockout
|2 MeSH
650 _ 2 |a Mitochondria: drug effects
|2 MeSH
650 _ 2 |a Mitochondria: enzymology
|2 MeSH
650 _ 2 |a Mitochondria: metabolism
|2 MeSH
650 _ 2 |a Oxidation-Reduction
|2 MeSH
650 _ 2 |a Oxidative Stress: drug effects
|2 MeSH
650 _ 2 |a Parkinson Disease: enzymology
|2 MeSH
650 _ 2 |a Parkinson Disease: genetics
|2 MeSH
650 _ 2 |a Parkinson Disease: metabolism
|2 MeSH
650 _ 2 |a Protein Deglycase DJ-1: genetics
|2 MeSH
650 _ 2 |a Substantia Nigra: enzymology
|2 MeSH
650 _ 2 |a Substantia Nigra: metabolism
|2 MeSH
650 _ 2 |a Tacrolimus: pharmacology
|2 MeSH
650 _ 2 |a alpha-Synuclein: metabolism
|2 MeSH
700 1 _ |a Song, Pingping
|0 P:(DE-HGF)0
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700 1 _ |a Mazzulli, Joseph R
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700 1 _ |a Zampese, Enrico
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700 1 _ |a Wong, Yvette C
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700 1 _ |a Jeon, Sohee
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700 1 _ |a Santos, David P
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700 1 _ |a Blanz, Judith
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700 1 _ |a Obermaier, Carolin D
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700 1 _ |a Strojny, Chelsee
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700 1 _ |a Savas, Jeffrey N
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700 1 _ |a Kiskinis, Evangelos
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700 1 _ |a Zhuang, Xiaoxi
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700 1 _ |a Krüger, Rejko
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700 1 _ |a Surmeier, D James
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700 1 _ |a Krainc, Dimitri
|0 P:(DE-HGF)0
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|e Corresponding author
773 1 8 |a 10.1126/science.aam9080
|b : American Association for the Advancement of Science (AAAS), 2017-09-07
|n 6357
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|t Science
|v 357
|y 2017
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773 _ _ |a 10.1126/science.aam9080
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