Mortalin: a protein associated with progression of Parkinson disease?
Parkinson disease (PD) is a progressive neurodegenerative disorder that is considered to affect the brainstem at its early stages and other brain regions, including the limbic system and isocortex, in advanced stages. It has been suggested that PD progression is characterized pathologically by the spreading of Lewy body deposition. To identify novel proteins involved in PD progression, we prepared subcellular fractions from the frontal cortex of pathologically verified PD patients at different stages of disease and Lewy body deposition and from age-matched controls. Protein expression profiles were compared using a robust quantitative proteomic technique called isobaric tagging for relative and absolute quantification in conjunction with mass spectrometry. Approximately 200 proteins were found to display significant differences in their relative abundance between PD patients at various stages and controls. Gene ontology analysis indicated that these altered proteins belonged to many categories (e.g. mitochondrial function and neurotransmission) that were likely critically involved in the pathogenesis of PD. Of those, mortalin, a mitochondrial protein, was decreased in the advanced PD cases and was further validated to be decreased using independent techniques. These results suggest a role for mortalin in PD progression.
Shi
Min
M
Department of Pathology, University of Washington, School of Medicine, Seattle, Washington, USA.
Jin
Jinghua
J
Wang
Yan
Y
Beyer
Richard P
RP
Kitsou
Efstathia
E
Albin
Roger L
RL
Gearing
Marla
M
Pan
Catherine
C
Zhang
Jing
J
D001921:Brain / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D018450:Disease Progression; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011180:Postmortem Changes; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013347:Subcellular Fractions / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D009419:Nerve Tissue Proteins; C080352:mortalin