Article (Scientific journals)
Balance is the challenge--the impact of mitochondrial dynamics in Parkinson's disease.
Burbulla, Lena F.; Krebiehl, Guido; Krüger, Rejko
2010In European Journal of Clinical Investigation, 40 (11), p. 1048-60
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Keywords :
Autophagy/genetics; Homeostasis/genetics; Humans; Mitochondria/genetics/metabolism; Oxidative Stress; Parkinson Disease/genetics/metabolism/physiopathology; Signal Transduction/genetics
Abstract :
[en] Impaired mitochondrial function has been implicated in neurodegeneration in Parkinson's disease (PD) based on biochemical and pathoanatomical studies in brains of PD patients. This observation was further substantiated by the identification of exogenic toxins, i.e. complex I inhibitors that directly affect mitochondrial energy metabolism and cause Parkinsonism in humans and various animal models. Recently, insights into the underlying molecular signalling pathways leading to alterations in mitochondrial homeostasis were gained based on the functional characterization of mitoprotective genes identified in rare forms of inherited PD. Using in vitro and in vivo loss of function models of the Parkin, PINK1, DJ-1 and Omi/HtrA2 gene, the emerging field of mitochondrial dynamics in PD was established as being critical for the maintenance of mitochondrial function in neurons. This underscored the concept that mitochondria are highly dynamic organelles, which are tightly regulated to continuously adapt shape to functional and anatomical requirements during axonal transport, synaptic signalling, organelle degradation and cellular energy supply. The dissection of pathways involved in mitochondrial quality control clearly established the PINK1/Parkin-pathway in the clearance of dysfunctional mitochondria by autophagy and hints to a complex interplay between PD-associated proteins acting at the mitochondrial interface. The elucidation of this mitoprotective signalling network may help to define novel therapeutic targets for PD via molecular modelling of mitochondria and/or pharmacological modulation of mitochondrial dynamics.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group)
Disciplines :
Genetics & genetic processes
Author, co-author :
Burbulla, Lena F.
Krebiehl, Guido
Krüger, Rejko ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Language :
English
Title :
Balance is the challenge--the impact of mitochondrial dynamics in Parkinson's disease.
Publication date :
2010
Journal title :
European Journal of Clinical Investigation
ISSN :
1365-2362
Publisher :
Blackwell, Oxford, United Kingdom
Volume :
40
Issue :
11
Pages :
1048-60
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c) 2010 The Authors. European Journal of Clinical Investigation (c) 2010 Stichting European Society for Clinical Investigation Journal Foundation.
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