Rare Diseases Symptoms Automatic Extraction

Small molecule inhibition of p38 MAP kinase extends the replicative life span of human ATR-Seckel syndrome fibroblasts.

[werner syndrome]

Ataxia-telangiectasia and rad3 (ATR)-related Seckel syndrome is associated with growth retardation and premature aging features. ATR-Seckel fibroblasts have a reduced replicative capacity in vitro and an aged morphology that is associated with activation of stress-associated p38 mitogen-activated protein kinase and phosphorylated HSP27. These phenotypes are prevented using p38 inhibitors, with replicative capacity restored to the normal range. However, this stressed phenotype is retained in telomerase-immortalized ATR-Seckel fibroblasts, indicating that it is independent of telomere erosion. As with normal fibroblasts, senescence in ATR-Seckel is bypassed by p53 abrogation. Young ATR-Seckel fibroblasts show elevated levels of p21(WAF1), p16(INK4A), phosphorylated actin-binding protein cofilin, and phosphorylated caveolin-1, with small molecule drug inhibition of p38 reducing p16(INK4A) and caveolin-1 phosphorylation. In conclusion, ATR-Seckel fibroblasts undergo accelerated aging via stress-induced premature senescence and p38 activation that may underlie certain clinical features of Seckel syndrome, and our data suggest a novel target for pharmacological intervention in this human syndrome.

Diseases presenting "elevated levels" symptom

  • 22q11.2 deletion syndrome
  • adrenal incidentaloma
  • adrenomyeloneuropathy
  • alexander disease
  • aniridia
  • cadasil
  • canavan disease
  • congenital adrenal hyperplasia
  • epidermolysis bullosa simplex
  • erythropoietic protoporphyria
  • esophageal carcinoma
  • fabry disease
  • familial hypocalciuric hypercalcemia
  • hereditary cerebral hemorrhage with amyloidosis
  • inclusion body myositis
  • kabuki syndrome
  • omenn syndrome
  • phenylketonuria
  • primary effusion lymphoma
  • pyruvate dehydrogenase deficiency
  • scrub typhus
  • sneddon syndrome
  • werner syndrome
  • wiskott-aldrich syndrome
  • wolf-hirschhorn syndrome
  • x-linked adrenoleukodystrophy
  • zellweger syndrome

You can validate or delete this automatically detected symptom