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タイトル | Conformational change of α-synuclein fibrils in cerebrospinal fluid from different clinical phases of Parkinson's disease. |
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ジャーナル・号・ページ | Structure, Vol. 31, Issue 1, Page 78-87.e5, Year 2023 |
掲載日 | 2023年1月5日 |
著者 | Yun Fan / Yunpeng Sun / Wenbo Yu / Youqi Tao / Wencheng Xia / Yiqi Liu / Qinyue Zhao / Yilin Tang / Yimin Sun / Fengtao Liu / Qin Cao / Jianjun Wu / Cong Liu / Jian Wang / Dan Li / |
PubMed 要旨 | α-Synuclein (α-syn) has been shown to form various conformational fibrils associated with different synucleinopathies. But whether the conformation of α-syn fibrils changes during disease ...α-Synuclein (α-syn) has been shown to form various conformational fibrils associated with different synucleinopathies. But whether the conformation of α-syn fibrils changes during disease progression is unclear. Here, we amplified α-syn aggregates from the cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD) staged in preclinical PD (pre-PD), middle- to late-stage PD (mid-PD), and late-stage PD (late-PD). Our results show that α-syn fibrils derived from the late-PD patient are most potent in inducing endogenous α-syn aggregation in primary neurons, followed by the mid-PD and pre-PD fibrils. By using cryo-electron microscopy, we further determined the high-resolution structures of the CSF-amplified fibrils. The structures exhibit remarkable differences in a minor but significant population of conformational species in different staged samples. Our work demonstrates structural and pathological differences between α-syn fibrils derived from PD patients at a spectrum of clinical stages, which suggests potential conformational transition of α-syn fibrils during the progression of PD. |
リンク | Structure / PubMed:36513068 |
手法 | EM (らせん対称) |
解像度 | 2.6 - 3.4 Å |
構造データ | EMDB-31702, PDB-7v47: EMDB-31703, PDB-7v48: EMDB-31704, PDB-7v49: EMDB-33332, PDB-7xo0: EMDB-33333, PDB-7xo1: EMDB-33334, PDB-7xo2: EMDB-33335, PDB-7xo3: |
由来 |
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キーワード | PROTEIN FIBRIL / amyloid fibril |