Article (Scientific journals)
Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson's disease.
Burbulla, Lena F.; Song, Pingping; Mazzulli, Joseph R. et al.
2017In Science, 357 (6357), p. 1255-1261
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Keywords :
mitochondrial; lysosomal; parkinson's; dopaminergic; neurodegeneration; oxidation
Abstract :
[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.
Disciplines :
Neurology
Author, co-author :
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 ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Surmeier, D. James
Krainc, Dimitri
More authors (6 more) Less
External co-authors :
yes
Language :
English
Title :
Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson's disease.
Publication date :
22 September 2017
Journal title :
Science
ISSN :
1095-9203
Publisher :
American Association for the Advancement of Science, Washington, United States - District of Columbia
Volume :
357
Issue :
6357
Pages :
1255-1261
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
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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