Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease-Reference-Cited by-同舟云学术

Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease

Published:2017-09-22 Issue:6357 Volume:357 Page:1255-1261
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Burbulla Lena F.¹²^ORCID,Song Pingping¹,Mazzulli Joseph R.¹²^ORCID,Zampese Enrico³^ORCID,Wong Yvette C.¹^ORCID,Jeon Sohee¹,Santos David P.¹^ORCID,Blanz Judith¹^ORCID,Obermaier Carolin D.⁴⁵⁶^ORCID,Strojny Chelsee¹^ORCID,Savas Jeffrey N.¹,Kiskinis Evangelos¹^ORCID,Zhuang Xiaoxi⁷^ORCID,Krüger Rejko⁴⁶⁸^ORCID,Surmeier D. James³,Krainc Dimitri¹²^ORCID

Affiliation:

1. Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

2. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegeneration, Charlestown, MA 02129, USA.

3. Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

4. Department for Neurodegenerative Diseases and Hertie-Institute for Clinical Brain Research, University of Tübingen, DZNE, German Centre for Neurodegenerative Diseases, Tübingen, Germany.

5. Graduate School for Cellular and Molecular Neuroscience, University of Tübingen, Germany.

6. Clinical and Experimental Neuroscience, Luxembourg Center for Systems Biomedicine, University of Luxembourg, Luxembourg.

7. Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA.

8. Centre Hospitalier Luxembourg, Luxembourg.

Abstract

Human-derived neurons provide the answers Pathways involved in energy metabolism and removal of cellular debris by lysosomes play an important role in protecting our brain from degeneration in Parkinson's disease. Burbulla et al. identified a toxic cascade of mitochondrial and lysosomal dysfunction in human neurons derived from patients with Parkinson's. The dysfunction was mediated by accumulation of oxidized dopamine and α-synuclein, but it was not found in Parkinson's mouse models, owing to species-specific differences in dopamine metabolism. Inherent species-specific differences between human and mouse neurons emphasize the value of studying human neurons to identify relevant targets for treatment of Parkinson's disease and related synucleinopathies. Science , this issue p. 1255

Funder

NIH Office of the Director

IDP Foundation

Michael J. Fox Foundation for Parkinson’s Research

JPB Foundation

NIH

German Academic Exchange Service

Spinal Muscular Atrophy Foundation

Les Turner ALS Foundation

Target ALS

Publisher

American Association for the Advancement of Science (AAAS)