8A9L

Cryo-EM structure of alpha-synuclein filaments from Parkinson's disease and dementia with Lewy bodies

8A9L の概要

• エントリーDOI: 10.2210/pdb8a9l/pdb
• EMDBエントリー: 15285
• 分子名称: Alpha-synuclein, Unknown fragment, ... (4 entities in total)
• 機能のキーワード: alpha-synuclein, amyloid, fibril, parkinson's disease (pd), parkinson's disease dementia (pdd), dementia with lewy bodies (dlb), synucleinopathy, protein fibril
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 15887.84

構造登録者

Yang, Y.,Shi, Y.,Schweighauser, M.,Zhang, X.J.,Kotecha, A.,Murzin, A.G.,Garringer, H.J.,Cullinane, P.,Saito, Y.,Foroud, T.,Warner, T.T.,Hasegawa, K.,Vidal, R.,Murayama, S.,Revesz, T.,Ghetti, B.,Hasegawa, M.,Lashley, T.,Scheres, H.W.S.,Goedert, M. (登録日: 2022-06-28, 公開日: 2022-08-31, 最終更新日: 2024-07-24)

主引用文献

Yang, Y.,Shi, Y.,Schweighauser, M.,Zhang, X.,Kotecha, A.,Murzin, A.G.,Garringer, H.J.,Cullinane, P.W.,Saito, Y.,Foroud, T.,Warner, T.T.,Hasegawa, K.,Vidal, R.,Murayama, S.,Revesz, T.,Ghetti, B.,Hasegawa, M.,Lashley, T.,Scheres, S.H.W.,Goedert, M.
Structures of alpha-synuclein filaments from human brains with Lewy pathology.
Nature, 610:791-795, 2022

PubMed Abstract: Parkinson's disease (PD) is the most common movement disorder, with resting tremor, rigidity, bradykinesia and postural instability being major symptoms. Neuropathologically, it is characterized by the presence of abundant filamentous inclusions of α-synuclein in the form of Lewy bodies and Lewy neurites in some brain cells, including dopaminergic nerve cells of the substantia nigra. PD is increasingly recognised as a multisystem disorder, with cognitive decline being one of its most common non-motor symptoms. Many patients with PD develop dementia more than 10 years after diagnosis. PD dementia (PDD) is clinically and neuropathologically similar to dementia with Lewy bodies (DLB), which is diagnosed when cognitive impairment precedes parkinsonian motor signs or begins within one year from their onset. In PDD, cognitive impairment develops in the setting of well-established PD. Besides PD and DLB, multiple system atrophy (MSA) is the third major synucleinopathy. It is characterized by the presence of abundant filamentous α-synuclein inclusions in brain cells, especially oligodendrocytes (Papp-Lantos bodies). We previously reported the electron cryo-microscopy structures of two types of α-synuclein filament extracted from the brains of individuals with MSA. Each filament type is made of two different protofilaments. Here we report that the cryo-electron microscopy structures of α-synuclein filaments from the brains of individuals with PD, PDD and DLB are made of a single protofilament (Lewy fold) that is markedly different from the protofilaments of MSA. These findings establish the existence of distinct molecular conformers of assembled α-synuclein in neurodegenerative disease.

PubMed: 36108674
DOI: 10.1038/s41586-022-05319-3

実験手法

ELECTRON MICROSCOPY (2.2 Å)