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- Title
Targeting of NAT10 enhances healthspan in a mouse model of human accelerated aging syndrome.
- Authors
Balmus, Gabriel; Larrieu, Delphine; Barros, Ana C.; Collins, Casey; Abrudan, Monica; Demir, Mukerrem; Geisler, Nicola J.; Lelliott, Christopher J.; White, Jacqueline K.; Karp, Natasha A.; Atkinson, James; Kirton, Andrea; Jacobsen, Matt; Clift, Dean; Rodriguez, Raphael; Adams, David J.; Jackson, Stephen P.
- Abstract
Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare, but devastating genetic disease characterized by segmental premature aging, with cardiovascular disease being the main cause of death. Cells from HGPS patients accumulate progerin, a permanently farnesylated, toxic form of Lamin A, disrupting the nuclear shape and chromatin organization, leading to DNA-damage accumulation and senescence. Therapeutic approaches targeting farnesylation or aiming to reduce progerin levels have provided only partial health improvements. Recently, we identified Remodelin, a small-molecule agent that leads to amelioration of HGPS cellular defects through inhibition of the enzyme N-acetyltransferase 10 (NAT10). Here, we show the preclinical data demonstrating that targeting NAT10 in vivo, either via chemical inhibition or genetic depletion, significantly enhances the healthspan in a LmnaG609G HGPS mouse model. Collectively, the data provided here highlights NAT10 as a potential therapeutic target for HGPS.
- Subjects
PROGERIA; PREMATURE aging (Medicine); MICE; GENETIC disorders; NUCLEAR shapes
- Publication
Nature Communications, 2018, Vol 9, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-03770-3