Sirt6 Mono‐ADP‐Ribosylates YY1 to Promote Dystrophin Expression for Neuromuscular Transmission
Abstract: The degeneration of the neuromuscular junction (NMJ) and the decline in motor function are common features of aging, but the underlying mechanisms have remained largely unclear. This study reveals that Sirt6 is reduced in aged mouse muscles. Ablation of Sirt6 in skeletal muscle causes a reduction of Dystrophin levels, resulting in premature NMJ degeneration, compromised neuromuscular transmission, and a deterioration in motor performance. Mechanistic studies show that Sirt6 negatively regulates the stability of the Dystrophin repressor YY1 (Yin Yang 1). Specifically, Sirt6 mono‐ADP‐ribosylates YY1, causing its disassociation from the Dystrophin promoter and allowing YY1 to bind to the SMURF2 E3 ligase, leading to its degradation. Importantly, supplementation with nicotinamide mononucleotide (NMN) enhances the mono‐ADP‐ribosylation of YY1 and effectively delays NMJ degeneration and the decline in motor function in elderly mice. These findings provide valuable insights into the intricate mechanisms underlying NMJ degeneration during aging. Targeting Sirt6 could be a potential therapeutic approach to mitigate the detrimental effects on NMJ degeneration and improve motor function in the elderly population.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Sirt6 Mono‐ADP‐Ribosylates YY1 to Promote Dystrophin Expression for Neuromuscular Transmission ; day:10 ; month:10 ; year:2024 ; extent:16
Advanced science ; (10.10.2024) (gesamt 16)
- Urheber
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Zhang, Wei
Bai, Lei
Xu, Wentao
Liu, Jun
Chen, Yi
Lin, Weiqiang
Lu, Huasong
Wang, Binwei
Luo, Benyan
Peng, Guoping
Zhang, Kejing
Shen, Chengyong
- DOI
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10.1002/advs.202406390
- URN
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urn:nbn:de:101:1-2410101429001.593237059186
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:36 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Zhang, Wei
- Bai, Lei
- Xu, Wentao
- Liu, Jun
- Chen, Yi
- Lin, Weiqiang
- Lu, Huasong
- Wang, Binwei
- Luo, Benyan
- Peng, Guoping
- Zhang, Kejing
- Shen, Chengyong
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