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Cofilin 1 promotes the pathogenicity and transmission of pathological α-synuclein in mouse models of Parkinson’s disease
The pathological hallmark of Parkinson’s disease (PD) is the presence of Lewy bodies (LBs) with aggregated α-synuclein being the major component. The abnormal α-synuclein aggregates transfer between cells, recruit endogenous α-synuclein into toxic LBs, and finally trigger neuronal injury. However, t...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748615/ https://www.ncbi.nlm.nih.gov/pubmed/35013321 http://dx.doi.org/10.1038/s41531-021-00272-w |
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author | Yan, Mingmin Xiong, Min Dai, Lijun Zhang, Xingyu Zha, Yunhong Deng, Xiaorong Yu, Zhui Zhang, Zhentao |
author_facet | Yan, Mingmin Xiong, Min Dai, Lijun Zhang, Xingyu Zha, Yunhong Deng, Xiaorong Yu, Zhui Zhang, Zhentao |
author_sort | Yan, Mingmin |
collection | PubMed |
description | The pathological hallmark of Parkinson’s disease (PD) is the presence of Lewy bodies (LBs) with aggregated α-synuclein being the major component. The abnormal α-synuclein aggregates transfer between cells, recruit endogenous α-synuclein into toxic LBs, and finally trigger neuronal injury. However, the molecular mechanisms mediating the aggregation and transmission of pathological α-synuclein remain unknown. Previously we found that cofilin 1, a member of the actin-binding protein, promotes the aggregation and pathogenicity of α-synuclein in vitro. Here we further investigated the effect of cofilin 1 in mouse models of PD. We found that the mixed fibrils composed of cofilin 1 and α-synuclein are more pathogenic to mice and more prone to propagation than pure α-synuclein fibrils. Overexpression of cofilin 1 enhances the seeding and spreading of α-synuclein aggregates, and induces PD-like behavioral impairments in mice. Together, these results illustrate the important role of cofilin 1 in the pathogenicity and transmission of α-synuclein during the onset and progression of PD. |
format | Online Article Text |
id | pubmed-8748615 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-87486152022-01-20 Cofilin 1 promotes the pathogenicity and transmission of pathological α-synuclein in mouse models of Parkinson’s disease Yan, Mingmin Xiong, Min Dai, Lijun Zhang, Xingyu Zha, Yunhong Deng, Xiaorong Yu, Zhui Zhang, Zhentao NPJ Parkinsons Dis Article The pathological hallmark of Parkinson’s disease (PD) is the presence of Lewy bodies (LBs) with aggregated α-synuclein being the major component. The abnormal α-synuclein aggregates transfer between cells, recruit endogenous α-synuclein into toxic LBs, and finally trigger neuronal injury. However, the molecular mechanisms mediating the aggregation and transmission of pathological α-synuclein remain unknown. Previously we found that cofilin 1, a member of the actin-binding protein, promotes the aggregation and pathogenicity of α-synuclein in vitro. Here we further investigated the effect of cofilin 1 in mouse models of PD. We found that the mixed fibrils composed of cofilin 1 and α-synuclein are more pathogenic to mice and more prone to propagation than pure α-synuclein fibrils. Overexpression of cofilin 1 enhances the seeding and spreading of α-synuclein aggregates, and induces PD-like behavioral impairments in mice. Together, these results illustrate the important role of cofilin 1 in the pathogenicity and transmission of α-synuclein during the onset and progression of PD. Nature Publishing Group UK 2022-01-10 /pmc/articles/PMC8748615/ /pubmed/35013321 http://dx.doi.org/10.1038/s41531-021-00272-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Yan, Mingmin Xiong, Min Dai, Lijun Zhang, Xingyu Zha, Yunhong Deng, Xiaorong Yu, Zhui Zhang, Zhentao Cofilin 1 promotes the pathogenicity and transmission of pathological α-synuclein in mouse models of Parkinson’s disease |
title | Cofilin 1 promotes the pathogenicity and transmission of pathological α-synuclein in mouse models of Parkinson’s disease |
title_full | Cofilin 1 promotes the pathogenicity and transmission of pathological α-synuclein in mouse models of Parkinson’s disease |
title_fullStr | Cofilin 1 promotes the pathogenicity and transmission of pathological α-synuclein in mouse models of Parkinson’s disease |
title_full_unstemmed | Cofilin 1 promotes the pathogenicity and transmission of pathological α-synuclein in mouse models of Parkinson’s disease |
title_short | Cofilin 1 promotes the pathogenicity and transmission of pathological α-synuclein in mouse models of Parkinson’s disease |
title_sort | cofilin 1 promotes the pathogenicity and transmission of pathological α-synuclein in mouse models of parkinson’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748615/ https://www.ncbi.nlm.nih.gov/pubmed/35013321 http://dx.doi.org/10.1038/s41531-021-00272-w |
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