臨床神経学

<シンポジウム35―4>運動ニューロン疾患の分子病態の解明と治療法開発への展望

ALSにおけるグリア関連病態

山中 宏二

理化学研究所脳科学総合研究センター・運動ニューロン変性研究チーム〔〒351―0198 埼玉県和光市広沢2―1〕

Dominant mutations in the Cu/Zn superoxide dismutase (SOD1) gene lead to a familial form of amyotrophic lateral sclerosis (ALS). Although ubiquitous expression of mutant SOD1 provokes progressive, selective motor neuron degeneration in human and rodents due to an acquired toxic property (ies) of the mutant, genetic and chimeric mice studies using SOD1 models indicate that non-neuronal cells play important roles in neurodegeneration through non-cell autonomous mechanism. Recent discovery of TDP-43 protein accumulation as a pathological hallmark of sporadic ALS suggested that the mechanisms of neurodegeneration in SOD1-linked familial ALS and sporadic ALS may be distinct. This prompted us to test whether SOD1-ALS and sporadic ALS share the common disease mechanisms in glial cells. To address this question, we have compared gene expression profile of spinal cords of SOD1 mice and sporadic ALS patients by establishing the cell-type specific transcriptome. Significant overlap of misregulated genes enriched in microglia was observed in sporadic ALS and SOD1 mouse models. The pathway analysis indicated the innate immune system, NF-kappaB signaling, and caspase-interleukin cascade that were misregulated in glial cells, suggesting these pathways may be the potential targets for disease modifying therapy of ALS.
Full Text of this Article in Japanese PDF (179K)

(臨床神経, 51:1192−1194, 2011)
key words:筋萎縮性側索硬化症,グリア,SOD1

(受付日:2011年5月20日)