Preserved structural property after amplification of alpha-synuclein aggregates from brains of synucleinopathies

• Main Authors: 吉永 早希, Saki Yoshinaga
• Format: Others
• Language: en
• Published: 2020
• Subjects: alpha-synuclein; synucleinopathy; seeding reaction; protein misfolding cyclic amplification(PMCA); mass spectrometry
• Online Access: https://doshisha.repo.nii.ac.jp/?action=repository_uri&item_id=1624; http://id.nii.ac.jp/1707/00001616/; https://doshisha.repo.nii.ac.jp/?action=repository_action_common_download&item_id=1624&item_no=1&attribute_id=21&file_no=1; https://doshisha.repo.nii.ac.jp/?action=repository_action_common_download&item_id=1624&item_no=1&attribute_id=21&file_no=2

神経変性疾患で蓄積する異常タンパク質の1つであるα-synは、PD、DLBおよびMSAの脳内に主に蓄積する。DLBやMSAの患者脳から解析可能な量のα-syn凝集体の増幅に成功した。増幅前後の凝集体のプロテイナーゼKコアのMS分析結果から、増幅による変化はないもののマウスとヒトのα-syn凝集体で切断パターンが異なることがわかった。これらの結果から、この方法が神経変性疾患の異常タンパク質研究の発展に貢献できることを示唆した。 === Pathological proteins related to neurodegenerative diseases are misfolded, aggregating to form amyloid fibrils. One of the pathological proteins, α-syn, accumulates in the brains of PD, DLB and MSA. We first performed amplification of α-syn aggregates. We successfully amplified enough α-syn aggregates derived from α-syncleinopathies. We found that the MS analysis results of proteinase K-resistant cores of the aggregates before and after the amplification differ between mouse and human α-syn aggregates. The results suggest that structural properties of amplified α-syn fibrils are preserved and these methods can be applicable in the study of pathological proteins of the neurodegenerative disorders. === 博士(理学) === Doctor of Philosophy in Science === 同志社大学 === Doshisha University