異常蛋白質のプリオン様伝播—現状とこれからの課題

The Prion-like Mechanism in Neurodegenerative Diseases-Current Studies and Future Prospects

プリオン様異常蛋白質の脳内伝播は，アルツハイマー病，パーキンソン病など，疾患ごとに特定の異常蛋白質が蓄積する主要な神経変性疾患の発症，進行の根底にあるメカニズムと考えられる。疾患の多様性，回路選択的変性，病気の進行性は，このプリオン様の異常蛋白質の自己複製的な増幅，伝播，「strain」の違いで説明が可能である。そのメカニズムの解明と伝播を抑制する薬剤などの探索が今後の治療法開発に重要である。

Abstract

Intracellular abnormal protein deposits, such as tau, α-synuclein and TDP-43, are the hallmark of many neurodegenerative diseases, and the distributions of these pathological proteins are closely correlated with disease symptoms and progression. A growing body of evidence strongly suggests that these abnormal proteins have prion-like properties: they convert normal proteins into abnormal forms, self-propagate through neuronal networks, and then spread in the brain. This prion-like propagation of abnormal proteins may account for the diversity, selective degeneration and disease progression seen in neurodegenerative diseases, although the molecular mechanism remains uncertain the molecular details of this mechanism. This review describes recent studies on prion-like properties of abnormal proteins in vitro, in cells and in animal experimental models.