In:
Nature Communications, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2018-04-27)
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 Lmna G609G HGPS mouse model. Collectively, the data provided here highlights NAT10 as a potential therapeutic target for HGPS.
Type of Medium:
Online Resource
ISSN:
2041-1723
DOI:
10.1038/s41467-018-03770-3
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2018
detail.hit.zdb_id:
2553671-0