臨床神経学

<シンポジウム(2)―11―4>アルツハイマー病の新展開―分子病態から治療戦略へ

アルツハイマー病とタウ蛋白

田中 稔久, 丸山 大輔, 武田 雅俊

大阪大学大学院医学系研究科・精神医学〔〒565―0871 大阪府吹田市山田丘2―2,D3〕

To elucidate involvement of tau protein in neurodegenerative processes in Alzheimer disease and related disorders, self-assembly process and degradative process of tau protein were examined. To understand the mechanisms of the aggregation, binding affinity of tau protein to 14-3-3 protein, which converts tau to a filamentous or aggregated form. was investigated employing a surface plasmon resonance assay. Phosphorylation of tau by protein kinase A increased affinity of tau to 14-3-3, whereas the phosphorylation attenuated formation of filaments or aggregates. FTDP-17 mutation increased affinity of unphosphorlated tau to 14-3-3, compared to wild typed unphosphorylated tau. However the phosphorylation increased its affinity further to the similar level of the affinity of phosphorylated wild typed tau. Similarly the phosphorylation also attenuated formation of filaments or aggreeagates from FTDP-17 mutated tau. To understand the mechanisms of the intracellular accumulation, possible involvement of proteases were studied. Among several proteases, puromycin-sensitive aminopeptidase (PSA) was found as a predominant regulator of degradation of tau protein. In addition FTDP-17 mutation increased phosphorylation of tau proten in cells, and attenuated intracellular degradation of tau protein. These results suggest that self-assembly and accumulation of tau protein are regulated by phosphorylation, and FTDP-17 mutation affects those complexed processes.
Full Text of this Article in Japanese PDF (168K)

(臨床神経, 52:1171−1173, 2012)
key words:タウ蛋白,アルツハイマー病,リン酸化,14-3-3蛋白,puromycin-sensitive aminopeptidase(PSA)

(受付日:2012年5月24日)