Reference : Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson's di...
Scientific journals : Article
Human health sciences : Neurology
http://hdl.handle.net/10993/32460
Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson's disease.
English
Burbulla, Lena F. [> >]
Song, Pingping [> >]
Mazzulli, Joseph R. [> >]
Zampese, Enrico [> >]
Wong, Yvette C. [> >]
Jeon, Sohee [> >]
Santos, David P. [> >]
Blanz, Judith [> >]
Obermaier, Carolin D. [> >]
Strojny, Chelsee [> >]
Savas, Jeffrey N. [> >]
Kiskinis, Evangelos [> >]
Zhuang, Xiaoxi [> >]
Krüger, Rejko mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit]
Surmeier, D. James [> >]
Krainc, Dimitri [> >]
22-Sep-2017
Science (New York, N.Y.)
357
6357
1255-1261
Yes (verified by ORBilu)
International
0036-8075
1095-9203
United States
[en] mitochondrial ; lysosomal ; parkinson's ; dopaminergic ; neurodegeneration ; oxidation
[en] 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 alpha-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 alpha-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.
http://hdl.handle.net/10993/32460
Copyright (c) 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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