αシヌクレイン細胞間伝播を標的としたシヌクレイノパチー疾患修飾療法の開発

Targeting Transcellular Transport of α-Synuclein for Developing Disease-Modifying Therapies for Synucleinopathy

パーキンソン病に対するドパミン補充療法は，神経疾患治療史における偉大なマイルストーンである一方，その効果に限界があることも事実である。ゆえに，病態の鍵となるαシヌクレインの脳内蓄積を阻止する進行抑制治療の必要性が唱えられている。近年，αシヌクレインがプリオンのように細胞間を伝播し周辺へと病変を拡大させる細胞非自律的な病態機序が明らかとなってきた。プリオン様伝播は疾患修飾療法の標的として注目されている。

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder and it is characterized by progressive physical disability along with a variety of non-motor symptoms. Drugs that replenish dopamine can partly alleviate the motor symptoms; however, they do not cure the disease itself. Therefore, there is an urgent need for disease modifying therapies that would delay or prevent neurodegeneration. Increasing evidence suggests that α-synuclein, a key molecule in PD, is secreted into the extracellular environment and can be transported from cell-to-cell, thereby affecting the physiological state of the neighboring cells in a prion-like manner. Given the potential role of extracellular α-synuclein as the cause of disease progression, its prion-like propagation is a promising target for developing disease-modifying therapies for PD and other synucleinopathies.