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从患者来源的路易小体中扩增的α-突触核蛋白聚集物在小鼠中再现了路易体疾病。

α-Synuclein aggregates amplified from patient-derived Lewy bodies recapitulate Lewy body diseases in mice.

机构信息

Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104-2676, USA.

Department of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, Tokyo, Japan.

出版信息

Nat Commun. 2023 Oct 28;14(1):6892. doi: 10.1038/s41467-023-42705-5.

DOI:10.1038/s41467-023-42705-5
PMID:37898614
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10613245/
Abstract

Extraction of α-Synuclein (αSyn) aggregates from Lewy body disease (LBD) brains has been widely described yet templated fibrillization of LB-αSyn often fails to propagate its structural and functional properties. We recently demonstrated that aggregates amplified from LB-αSyn (ampLB) show distinct biological activities in vitro compared to human αSyn preformed fibrils (hPFF) formed de novo. Here we compare the in vivo biological activities of hPFF and ampLB regarding seeding activity, latency in inducing pathology, distribution of pathology, inclusion morphology, and cell-type preference. Injection of ampLB into mice expressing only human αSyn (male Thy1:SNCA/Snca mice) induced pathologies similar to those of LBD subjects that were distinct from those induced by hPFF-injection or developing spontaneously with aging. Importantly, αSyn aggregates in ampLB-injected Thy1:SNCA/Snca mice maintained the unique biological and conformational features of original LB-αSyn. These results indicate that ampLB-injection, rather than conventional PFF-injection or αSyn overexpression, faithfully models key aspects of LBD.

摘要

从路易体病 (LBD) 大脑中提取α-突触核蛋白 (αSyn) 聚集体已被广泛描述，但 LB-αSyn 的模板纤维化往往无法传播其结构和功能特性。我们最近证明，从 LB-αSyn 中扩增的聚集体 (ampLB) 在体外表现出与从头形成的人 αSyn 原纤维 (hPFF) 不同的生物学活性。在这里，我们比较了 hPFF 和 ampLB 在种子活性、诱导病理学潜伏期、病理学分布、包含形态和细胞类型偏好方面的体内生物学活性。将 ampLB 注射到仅表达人 αSyn 的小鼠体内 (雄性 Thy1:SNCA/Snca 小鼠) 会诱导出类似于 LBD 患者的病理学，与 hPFF 注射或随年龄自然发展引起的病理学不同。重要的是，ampLB 注射诱导的 Thy1:SNCA/Snca 小鼠中的 αSyn 聚集体保持了原始 LB-αSyn 的独特生物学和构象特征。这些结果表明，ampLB 注射而不是传统的 PFF 注射或 αSyn 过表达能够忠实地模拟 LBD 的关键方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdd3/10613245/73ccff8078c5/41467_2023_42705_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdd3/10613245/1c51017bf6e5/41467_2023_42705_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdd3/10613245/e1ada0450972/41467_2023_42705_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdd3/10613245/cefa57add1b2/41467_2023_42705_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdd3/10613245/51f8739af4b6/41467_2023_42705_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdd3/10613245/11d383f3f751/41467_2023_42705_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdd3/10613245/73ccff8078c5/41467_2023_42705_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdd3/10613245/1c51017bf6e5/41467_2023_42705_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdd3/10613245/f6fbe6e40cd6/41467_2023_42705_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdd3/10613245/e1ada0450972/41467_2023_42705_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdd3/10613245/cefa57add1b2/41467_2023_42705_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdd3/10613245/51f8739af4b6/41467_2023_42705_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdd3/10613245/11d383f3f751/41467_2023_42705_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdd3/10613245/73ccff8078c5/41467_2023_42705_Fig7_HTML.jpg

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本文引用的文献

1
Structures of α-synuclein filaments from human brains with Lewy pathology.具有路易体病理的人脑α-突触核蛋白纤维的结构。
Nature. 2022 Oct;610(7933):791-795. doi: 10.1038/s41586-022-05319-3. Epub 2022 Sep 15.
2
Multiple system atrophy.多系统萎缩
Nat Rev Dis Primers. 2022 Aug 25;8(1):56. doi: 10.1038/s41572-022-00382-6.
3
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Potential common pathogenesis of several neurodegenerative diseases.
几种神经退行性疾病潜在的共同发病机制。
Neural Regen Res. 2026 Mar 1;21(3):972-988. doi: 10.4103/NRR.NRR-D-24-01054. Epub 2025 May 30.
4
Association between red cell distribution width/serum albumin ratio and Parkinson's disease.红细胞分布宽度/血清白蛋白比值与帕金森病之间的关联
Eur J Med Res. 2025 May 31;30(1):431. doi: 10.1186/s40001-025-02707-z.
5
Stress granules: emerging players in neurodegenerative diseases.应激颗粒：神经退行性疾病中的新角色。
Transl Neurodegener. 2025 May 12;14(1):22. doi: 10.1186/s40035-025-00482-9.
6
Sex Specific Effects of Environmental Toxin-Derived Alpha Synuclein on Enteric Neuronal-Epithelial Interactions.环境毒素衍生的α-突触核蛋白对肠神经元-上皮相互作用的性别特异性影响。
Neurogastroenterol Motil. 2025 Jul;37(7):e70046. doi: 10.1111/nmo.70046. Epub 2025 Apr 24.
7
Research models to study lewy body dementia.用于研究路易体痴呆的研究模型。
Mol Neurodegener. 2025 Apr 23;20(1):46. doi: 10.1186/s13024-025-00837-w.
8
Liganded magnetic nanoparticles for magnetic resonance imaging of α-synuclein.用于α-突触核蛋白磁共振成像的配体化磁性纳米颗粒。
NPJ Parkinsons Dis. 2025 Apr 23;11(1):88. doi: 10.1038/s41531-025-00918-z.
9
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Arch Pharm Res. 2025 Apr;48(4):333-350. doi: 10.1007/s12272-025-01538-0. Epub 2025 Apr 14.
10
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NPJ Parkinsons Dis. 2025 Feb 19;11(1):31. doi: 10.1038/s41531-025-00886-4.
Acta Neuropathol Commun. 2021 Nov 24;9(1):188. doi: 10.1186/s40478-021-01288-2.
4
Phenotypic manifestation of α-synuclein strains derived from Parkinson's disease and multiple system atrophy in human dopaminergic neurons.帕金森病和多系统萎缩中α-突触核蛋白菌株在人多巴胺能神经元中的表型表现。
Nat Commun. 2021 Jun 21;12(1):3817. doi: 10.1038/s41467-021-23682-z.
5
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FEBS Open Bio. 2021 Apr;11(4):999-1013. doi: 10.1002/2211-5463.13110. Epub 2021 Feb 24.
6
α-synuclein strains that cause distinct pathologies differentially inhibit proteasome.α-突触核蛋白菌株导致不同的病理差异抑制蛋白酶体。
Elife. 2020 Jul 22;9:e56825. doi: 10.7554/eLife.56825.
7
Structures of α-synuclein filaments from multiple system atrophy.多系统萎缩中α-突触核蛋白丝的结构。
Nature. 2020 Sep;585(7825):464-469. doi: 10.1038/s41586-020-2317-6. Epub 2020 May 27.
8
Identification of distinct pathological signatures induced by patient-derived α-synuclein structures in nonhuman primates.鉴定源自于患者α-突触核蛋白结构的不同病理特征在非人灵长类动物中的诱导作用。
Sci Adv. 2020 May 13;6(20):eaaz9165. doi: 10.1126/sciadv.aaz9165. eCollection 2020 May.
9
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Brain. 2020 May 1;143(5):1462-1475. doi: 10.1093/brain/awaa096.
10
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Acta Neuropathol. 2020 Jun;139(6):977-1000. doi: 10.1007/s00401-020-02157-3. Epub 2020 Apr 30.