|
Progeria
|
0.800 |
Biomarker
|
disease |
BEFREE |
Defects in prelamin A processing by ZMPSTE24 result in premature aging disorders including Hutchinson Gilford Progeria Syndrome (HGPS) and related progeroid diseases.
|
30625386 |
2019 |
|
Progeria
|
0.800 |
Biomarker
|
disease |
BEFREE |
Mice deficient in zinc metalloproteinase STE24 (<i>Zmpste24</i><sup>-/-</sup>) exhibit premature age-related musculoskeletal pathologies similar to those observed in children with Hutchinson-Gilford progeria syndrome (HGPS).
|
31312666 |
2019 |
|
Progeria
|
0.800 |
Biomarker
|
disease |
BEFREE |
<b>Abbreviations:</b> HGPS: Hutchinson-Gilford progeria syndrome; ZMPSTE24: Zinc metallopeptidase STE24; FTI: Farnesyltransferase inhibitors; VSMCs: Vascular smooth muscle cells; iPSC: Induced pluripotent stem cells; EC: Endothelial cells; hTERT: Human telomerase reverse transcriptase; VEGF: vascular endothelial growth factor; DAF-FM DA: 3-Amino, 4-aminomethyl-2',7'-difluorofluorescein diacetate; BMP4: Bone Morphogenetic Protein 4; mmqPCR: mono chrome multiplex PCR; SCG: single-copy gene; CSI: Cell shape index.
|
31411525 |
2019 |
|
Progeria
|
0.800 |
Biomarker
|
disease |
BEFREE |
Moreover, in vivo analysis of the Zmpste24-/- HGPS mouse model demonstrates that treatment with a sclerostin-neutralizing antibody (SclAb), which targets an antagonist of canonical WNT/β-catenin signaling pathway, fully rescues the low bone mass phenotype to wild-type levels.
|
30001457 |
2018 |
|
Progeria
|
0.800 |
Biomarker
|
disease |
BEFREE |
Premature senescence can be induced by different stress factors and occurs in mouse embryonic fibroblasts (MEFs) derived from Zmpste24 metalloproteinase‑deficient mice, a progeria mouse model of Hutchinson‑Gilford Progeria Syndrome.
|
28990109 |
2017 |
|
Progeria
|
0.800 |
Biomarker
|
disease |
BEFREE |
Mutations in the nuclear membrane zinc metalloprotease ZMPSTE24 lead to diseases of lamin processing (laminopathies), such as the premature aging disease progeria and metabolic disorders.
|
23539603 |
2013 |
|
Progeria
|
0.800 |
Biomarker
|
disease |
BEFREE |
Several progeroid disorders, including Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (ZMPSTE24 deficiency), arise when a farnesylated and methylated form of prelamin A accumulates at the nuclear envelope.
|
23686339 |
2013 |
|
Progeria
|
0.800 |
Biomarker
|
disease |
BEFREE |
We examined the effect of progerin (an altered splicing product of the LMNA gene linked to Hutchinson Gilford progeria syndrome; HGPS) on the nuclear deformation of RCCs in comparison to that of HGPS cells.
|
24067370 |
2013 |
|
Progeria
|
0.800 |
Biomarker
|
disease |
BEFREE |
Failure to cleave the prelamin A "tail", due to mutations in either prelamin A or ZMPSTE24, results in a permanently prenylated form of prelamin A that underlies the premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS) and related progeroid disorders.
|
22355414 |
2012 |
|
Progeria
|
0.800 |
Biomarker
|
disease |
CTD_human |
Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria.
|
23217256 |
2012 |
|
Progeria
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
Here, we describe a progeroid syndrome that partially phenocopies Hutchinson-Gilford progeria syndrome (HGPS) but also exhibits distinctive features, including the absence of cardiovascular deficiencies characteristic of HGPS, the lack of mutations in LMNA and ZMPSTE24, and a relatively long lifespan of affected individuals.
|
21549337 |
2011 |
|
Progeria
|
0.800 |
Biomarker
|
disease |
BEFREE |
The premature aging phenotype of Hutchinson Gilford progeria syndrome is largely recapitulated in mice deficient for the lamin A-processing enzyme, Zmpste24.
|
21746928 |
2011 |
|
Progeria
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
Furthermore, by using progeroid mice deficient in ZMPSTE24 (zinc metalloprotease STE24 homologue) involved in lamin A maturation, we have demonstrated that, besides these abnormal cellular responses to stress, dysregulation of the somatotropic axis is responsible for some of the alterations associated with progeria.
|
22103512 |
2011 |
|
Progeria
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
We did not find a mutation in genes known to be associated with congenital lipodystrophy (APGAT2, BSCL2, CAV1, PTRF-CAVIN, PPARG, LMNB2) or with Hutchinson-Gilford progeria (ZMPSTE24, LMNA/C).
|
20979188 |
2010 |
|
Progeria
|
0.800 |
Biomarker
|
disease |
MGD |
Zmpste24-deficient mice exhibit multiple defects that phenocopy human accelerated aging processes such as Hutchinson-Gilford progeria syndrome.
|
20805469 |
2010 |
|
Progeria
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
Hutchinson-Gilford progeria syndrome (HGPS) patients are heterozygous for aLMNA gene mutation while Restrictive Dermopathy (RD) individuals have a homozygous deficiency in the processing protease Zmpste24.
|
19851476 |
2009 |
|
Progeria
|
0.800 |
Biomarker
|
disease |
BEFREE |
Here we report that the recruitment of DSB repair factors Rad50 and Rad51 to the DSB sites, as marked by gamma-H2AX, was impaired in human HGPS and Zmpste24-deficient cells.
|
17848622 |
2008 |
|
Progeria
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
To date, mutations in two genes, LMNA and ZMPSTE24, have been found in patients with HGPS.
|
17459035 |
2007 |
|
Progeria
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
Whereas the loss of function mutation of ZMPSTE24 normally results in lethal RD, the truncation of LMNA seems to be a salvage alteration alleviating the clinical picture to the HGPS phenotype.
|
16671095 |
2006 |
|
Progeria
|
0.800 |
Biomarker
|
disease |
MGD |
Nevertheless, an accumulation of farnesyl-prelamin A (as occurs with a deficiency in the prelamin A processing enzyme Zmpste24) caused dramatically misshapen nuclei and progeria-like disease phenotypes.
|
16511604 |
2006 |
|
Progeria
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
Hutchinson-Gilford progeria syndrome (HGPS; Online Mendelian Inheritance in Man accession no.
|
16461887 |
2006 |
|
Progeria
|
0.800 |
Biomarker
|
disease |
MGD |
We tested the efficacy of an FTI (ABT-100) in Zmpste24-deficient mice, a mouse model of progeria.
|
16484451 |
2006 |
|
Progeria
|
0.800 |
GermlineCausalMutation
|
disease |
ORPHANET |
Whereas the loss of function mutation of ZMPSTE24 normally results in lethal RD, the truncation of LMNA seems to be a salvage alteration alleviating the clinical picture to the HGPS phenotype.
|
16671095 |
2006 |
|
Progeria
|
0.800 |
Biomarker
|
disease |
BEFREE |
Finally, we draw attention to similarities in phenotype between FACE1-silenced HeLa cells and fibroblasts from patients with Hutchinson-Gilford progeria syndrome containing prelamin A mutations that prevent cleavage by the FACE1 endoprotease.
|
15671064 |
2005 |
|
Progeria
|
0.800 |
Biomarker
|
disease |
BEFREE |
A FTI also mislocalized prelamin A and improved nuclear shape in Zmpste24-deficient mouse embryonic fibroblasts (P < 0.0001) and improved nuclear shape in human HGPS fibroblasts (P < 0.0001).
|
16129834 |
2005 |