Mitochondrial dysfunction in mouse models of Parkinson's disease revealed by transcriptomics and proteomics.
It has been long thought that neuronal loss in Parkinson's disease (PD) is related to reactive oxygen species from mitochondrial dysfunction. However, there have been few investigations surveying both transcriptome and proteome in PD. This review focuses on recent work using microarrays and mass spectrometry to examine neurotoxicological models of PD in the mouse. Molecular pathways involved in oxidative phosphorylation, oxidative stress, apoptosis/cell death, signal transduction and neurotransmission were highlighted. Analysis of tyrosine nitration suggested that this important post-translational modification, due to conjugation of reactive oxygen species with nitric oxide, may play an important role in signal transduction as well as the molecular pathology of PD. Thus, the combined investigations highlight known pathways in PD but also point to new directions for research, implicating particularly the role of relatively understudied classes of post-translational modifications in normal cell signaling and neurological disorders.
Smith
Desmond J
DJ
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, CHS 23-120, Box 951735, Los Angeles, CA 90095-1735, USA. DSmith@mednet.ucla.edu
D000818:Animals; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D051379:Mice; D008928:Mitochondria / Q000473:pathology*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011499:Protein Processing, Post-Translational; D040901:Proteomics