Glial functions associated with pathogenesis of Parkinson's disease

Abstract

Since 1996, various responsible genes for familial Parkinson's including SNCA disease have been identified. Gene manipulation models for Parkinson disease (PD) have been developed, and a genotype–phenotype correlation has been explored with those PD models. Also, those models contributed to develop various promising therapies modulating alpha–synuclein expression levels, and some of them are in clinical trial phases.

Based on data of genetically manipulated models of neurodegenerative diseases, non–autonomous cell death associated with inflammation is recognized as an important pathogenesis of the diseases. In autopsied PD brains, increase of activated microglia as well as increased levels of inflammatory cytokines have been reported. Also, PET studies showed evidences of microglial activation in the brainstem. Also, the association of microglial function with alpha–synuclein has been proposed by PD models. We reviewed recent advances in molecular research on PD inflammation focusing on glial cells.