Progerin modulates the IGF-1R/Akt signaling involved in aging.
Progerin modulates the IGF-1R/Akt signaling involved in aging.
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DOI：
10.1126/sciadv.abo0322
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发表时间：
2022-07-08
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
作者：
Progerin, a product of LMNA mutation, leads to multiple nuclear abnormalities in patients with Hutchinson-Gilford progeria syndrome (HGPS), a devastating premature aging disorder. Progerin also accumulates during physiological aging. Here, we demonstrate that impaired insulin-like growth factor 1 receptor (IGF-1R)/Akt signaling pathway results in severe growth retardation and premature aging in Zmpste24−/− mice, a mouse model of progeria. Mechanistically, progerin mislocalizes outside of the nucleus, interacts with the IGF-1R, and down-regulates its expression, leading to inhibited mitochondrial respiration, retarded cell growth, and accelerated cellular senescence. Pharmacological treatment with the PTEN (phosphatase and tensin homolog deleted on chromosome 10) inhibitor bpV (HOpic) increases Akt activity and improves multiple abnormalities in Zmpste24-deficient mice. These findings provide previously unidentified insights into the role of progerin in regulating the IGF-1R/Akt signaling in HGPS and might be useful for treating LMNA-associated progeroid disorders. Progerin mislocalizes outside of the nucleus and impairs the IGF-1R/Akt signaling.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
3.5
作者：
Navarro, CL;Cadiñanos, J;Lévy, N
通讯作者：
Lévy, N
影响因子：
82.9
作者：
Liu, BH;Wang, JM;Zhou, ZJ
通讯作者：
Zhou, ZJ
影响因子：
64.8
作者：
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通讯作者：
Puigserver, Pere
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J