Restoring nuclear entry of Sirtuin 2 in oligodendrocyte progenitor cells promotes remyelination during ageing

Xiao Ru Ma; Xudong Zhu; Yujie Xiao; Hui Min Gu; Shuang Shuang Zheng; Liang Li; Fan Wang; Zhao Jun Dong; Di Xian Wang; Yang Wu; Chenyu Yang; Wenhong Jiang; Ke Yao; Yue Yin; Yang Zhang; Chao Peng; Lixia Gao; Zhuoxian Meng; Zeping Hu; Chong Liu; Li Li; Hou Zao Chen; Yousheng Shu; Zhenyu Ju; Jing Wei Zhao

doi:10.1038/s41467-022-28844-1

Restoring nuclear entry of Sirtuin 2 in oligodendrocyte progenitor cells promotes remyelination during ageing

Xiao Ru Ma, Xudong Zhu, Yujie Xiao, Hui Min Gu, Shuang Shuang Zheng, Liang Li, Fan Wang, Zhao Jun Dong, Di Xian Wang, Yang Wu, Chenyu Yang, Wenhong Jiang, Ke Yao, Yue Yin, Yang Zhang, Chao Peng, Lixia Gao, Zhuoxian Meng, Zeping Hu, Chong LiuLi Li, Hou Zao Chen, Yousheng Shu, Zhenyu Ju, Jing Wei Zhao

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31 Scopus citations

Abstract

The age-dependent decline in remyelination potential of the central nervous system during ageing is associated with a declined differentiation capacity of oligodendrocyte progenitor cells (OPCs). The molecular players that can enhance OPC differentiation or rejuvenate OPCs are unclear. Here we show that, in mouse OPCs, nuclear entry of SIRT2 is impaired and NAD⁺ levels are reduced during ageing. When we supplement β-nicotinamide mononucleotide (β-NMN), an NAD⁺ precursor, nuclear entry of SIRT2 in OPCs, OPC differentiation, and remyelination were rescued in aged animals. We show that the effects on myelination are mediated via the NAD⁺-SIRT2-H3K18Ac-ID4 axis, and SIRT2 is required for rejuvenating OPCs. Our results show that SIRT2 and NAD⁺ levels rescue the aged OPC differentiation potential to levels comparable to young age, providing potential targets to enhance remyelination during ageing.

Original language	English (US)
Article number	1225
Journal	Nature communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-28844-1
State	Published - Dec 2022
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Ma, X. R., Zhu, X., Xiao, Y., Gu, H. M., Zheng, S. S., Li, L., Wang, F., Dong, Z. J., Wang, D. X., Wu, Y., Yang, C., Jiang, W., Yao, K., Yin, Y., Zhang, Y., Peng, C., Gao, L., Meng, Z., Hu, Z., ... Zhao, J. W. (2022). Restoring nuclear entry of Sirtuin 2 in oligodendrocyte progenitor cells promotes remyelination during ageing. Nature communications, 13(1), Article 1225. https://doi.org/10.1038/s41467-022-28844-1

Ma, XR, Zhu, X, Xiao, Y, Gu, HM, Zheng, SS, Li, L, Wang, F, Dong, ZJ, Wang, DX, Wu, Y, Yang, C, Jiang, W, Yao, K, Yin, Y, Zhang, Y, Peng, C, Gao, L, Meng, Z, Hu, Z, Liu, C, Li, L, Chen, HZ, Shu, Y, Ju, Z & Zhao, JW 2022, 'Restoring nuclear entry of Sirtuin 2 in oligodendrocyte progenitor cells promotes remyelination during ageing', Nature communications, vol. 13, no. 1, 1225. https://doi.org/10.1038/s41467-022-28844-1

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title = "Restoring nuclear entry of Sirtuin 2 in oligodendrocyte progenitor cells promotes remyelination during ageing",

abstract = "The age-dependent decline in remyelination potential of the central nervous system during ageing is associated with a declined differentiation capacity of oligodendrocyte progenitor cells (OPCs). The molecular players that can enhance OPC differentiation or rejuvenate OPCs are unclear. Here we show that, in mouse OPCs, nuclear entry of SIRT2 is impaired and NAD+ levels are reduced during ageing. When we supplement β-nicotinamide mononucleotide (β-NMN), an NAD+ precursor, nuclear entry of SIRT2 in OPCs, OPC differentiation, and remyelination were rescued in aged animals. We show that the effects on myelination are mediated via the NAD+-SIRT2-H3K18Ac-ID4 axis, and SIRT2 is required for rejuvenating OPCs. Our results show that SIRT2 and NAD+ levels rescue the aged OPC differentiation potential to levels comparable to young age, providing potential targets to enhance remyelination during ageing.",

author = "Ma, {Xiao Ru} and Xudong Zhu and Yujie Xiao and Gu, {Hui Min} and Zheng, {Shuang Shuang} and Liang Li and Fan Wang and Dong, {Zhao Jun} and Wang, {Di Xian} and Yang Wu and Chenyu Yang and Wenhong Jiang and Ke Yao and Yue Yin and Yang Zhang and Chao Peng and Lixia Gao and Zhuoxian Meng and Zeping Hu and Chong Liu and Li Li and Chen, {Hou Zao} and Yousheng Shu and Zhenyu Ju and Zhao, {Jing Wei}",

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doi = "10.1038/s41467-022-28844-1",

language = "English (US)",

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AU - Ma, Xiao Ru

AU - Zhu, Xudong

AU - Xiao, Yujie

AU - Gu, Hui Min

AU - Zheng, Shuang Shuang

AU - Li, Liang

AU - Wang, Fan

AU - Dong, Zhao Jun

AU - Wang, Di Xian

AU - Wu, Yang

AU - Yang, Chenyu

AU - Jiang, Wenhong

AU - Yao, Ke

AU - Yin, Yue

AU - Zhang, Yang

AU - Peng, Chao

AU - Gao, Lixia

AU - Meng, Zhuoxian

AU - Hu, Zeping

AU - Liu, Chong

AU - Li, Li

AU - Chen, Hou Zao

AU - Shu, Yousheng

AU - Ju, Zhenyu

AU - Zhao, Jing Wei

PY - 2022/12

Y1 - 2022/12

N2 - The age-dependent decline in remyelination potential of the central nervous system during ageing is associated with a declined differentiation capacity of oligodendrocyte progenitor cells (OPCs). The molecular players that can enhance OPC differentiation or rejuvenate OPCs are unclear. Here we show that, in mouse OPCs, nuclear entry of SIRT2 is impaired and NAD+ levels are reduced during ageing. When we supplement β-nicotinamide mononucleotide (β-NMN), an NAD+ precursor, nuclear entry of SIRT2 in OPCs, OPC differentiation, and remyelination were rescued in aged animals. We show that the effects on myelination are mediated via the NAD+-SIRT2-H3K18Ac-ID4 axis, and SIRT2 is required for rejuvenating OPCs. Our results show that SIRT2 and NAD+ levels rescue the aged OPC differentiation potential to levels comparable to young age, providing potential targets to enhance remyelination during ageing.

AB - The age-dependent decline in remyelination potential of the central nervous system during ageing is associated with a declined differentiation capacity of oligodendrocyte progenitor cells (OPCs). The molecular players that can enhance OPC differentiation or rejuvenate OPCs are unclear. Here we show that, in mouse OPCs, nuclear entry of SIRT2 is impaired and NAD+ levels are reduced during ageing. When we supplement β-nicotinamide mononucleotide (β-NMN), an NAD+ precursor, nuclear entry of SIRT2 in OPCs, OPC differentiation, and remyelination were rescued in aged animals. We show that the effects on myelination are mediated via the NAD+-SIRT2-H3K18Ac-ID4 axis, and SIRT2 is required for rejuvenating OPCs. Our results show that SIRT2 and NAD+ levels rescue the aged OPC differentiation potential to levels comparable to young age, providing potential targets to enhance remyelination during ageing.

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Restoring nuclear entry of Sirtuin 2 in oligodendrocyte progenitor cells promotes remyelination during ageing

Abstract

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