Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms

In both genetic and idiopathic forms of Parkinson's disease (PD), considerable evidence supports the involvement of alpha-synuclein, electron transport chain complex 1, protein aggregation, and the ubiquitin-proteasome system. To investigate alterations in the transcription of genes that comprise these pathways, we performed gene expression profiling and functional gene group analysis of three brain regions (the substantia nigra, putamen, and area 9) in postmortem tissue from matched groups of PD or control subjects (n = 15/group). Verification of selected changes was performed using RT-PCR, and visualization of selected changes in expression was accomplished using in situ hybridization (ISH). Our results provide strong support for the impairment of multiple electron transport chain complexes and the ubiquitin-proteasomal system in PD, along with a robust induction of heat shock proteins and some anti-apoptotic gene groups. Several novel gene and gene group findings were also obtained that offer new insight into the pathogenesis and potential treatment of PD. (c) 2005 Wiley-Liss, Inc.