Parkinson's disease (PD) is the second most common neurodegenerative disorder and is characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta. To discover potential key molecules in this rocess, we utilized cDNA microarray technology to obtain an expression profile of transcripts in MN9D dopaminergic neuronal cells treated with 6-hydroxydopamine. Using a self-organizing map algorithm, data mining and clustering were combined to identify distinct functional subgroups of genes. We identified alterations in the expression of 81 genes in eight clusters. Among these genes, we verified protein expression patterns of MAP kinase phosphatase 1 and sequestosome 1 using both cell culture and rat brain models of PD. Immunological analyses revealed increased expression levels as well as aggregated distribution patterns of these gene products in 6-hydroxydopamine- treated dopaminergic neurons. In addition to the identification of ther proteins that are known to be associated with protein ggregation, our results raise the possibility that a more widespread set of proteins may be associated with the eneration of protein aggregates in dying neurons. Further research to determine the functional roles of other altered gene products within the same cluster as well as the seven remaining clusters may provide new insights into the neurodegeneration that underlies PD pathogenesis.
Bibliographical noteFunding Information:
The authors thank Dr. A. Heller for allowing us to use the MN9D cell line. This work was supported by a grant from the Ministry of Science and Technology through BRC, KOSEF (SRC, R11-2008-036-00000-0) and WCU (R33-2008-10014).
All Science Journal Classification (ASJC) codes
- Clinical Neurology
- Psychiatry and Mental health
- Biological Psychiatry