Werner Syndrome (Werner's Syndrome)

An autosomal recessive disorder that causes premature aging in adults, characterized by sclerodermal skin changes, cataracts, subcutaneous calcification, muscular atrophy, a tendency to diabetes mellitus, aged appearance of the face, baldness, and a high incidence of neoplastic disease.

Also Known As:

Networked: 749 relevant articles (14 outcomes, 46 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Insulin Resistance
2.	Diabetes Mellitus
3.	Neoplasms (Cancer)
4.	Leg Ulcer
5.	Chromosome Aberrations (Chromosome Abnormalities)

Experts

1.	Bohr, Vilhelm A: 57 articles (11/2019 - 04/2002)
2.	Opresko, Patricia L: 23 articles (08/2012 - 05/2003)
3.	Lebel, Michel: 21 articles (10/2021 - 01/2002)
4.	Davis, Terence: 19 articles (04/2016 - 04/2003)
5.	Kipling, David: 19 articles (04/2016 - 04/2003)
6.	Yokote, Koutaro: 18 articles (01/2022 - 09/2004)
7.	Goto, Makoto: 18 articles (01/2019 - 03/2003)
8.	Brosh, Robert M: 15 articles (01/2022 - 04/2002)
9.	Pichierri, Pietro: 14 articles (01/2022 - 03/2003)
10.	Bagley, Mark C: 14 articles (04/2016 - 11/2006)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Werner Syndrome:

1.	DNA (Deoxyribonucleic Acid)IBA 08/01/2022 - "Studies show that, apart from its vital role in repairing DNA damages, XPG is also responsible for R-loop formation, which facilitates exhibiting phenotypes of Werner Syndrome. " 12/17/2004 - "Studies of Werner syndrome cells and biochemical studies of WRN suggest that WRN plays a role in several DNA metabolic pathways. " 02/01/1987 - "[Studies on connective tissue biosynthesis and DNA synthesis of cultured dermal fibroblasts derived from patients with Werner's syndrome]." 06/01/2014 - "We generalize these simulations to Werner's syndrome, a condition in which large sections of DNA are removed during cell division and, amongst other conditions, results in rapid aging. " 06/01/2013 - "Deficiency in the helicase activity of the mutant may cause defects in replication and other DNA metabolic processes, which in turn could be responsible for the Werner syndrome phenotype in the patient. "
2.	EnzymesIBA 08/01/2000 - "Recent data suggest that the yeast enzyme Sgs1p, as well as two human homologues, which are encoded by the Bloom's and Werner's syndrome genes, function during DNA replication and possibly in a replication checkpoint specific to S phase." 05/01/1987 - "[Enzyme activities of cultured skin fibroblasts in Werner's syndrome]." 01/01/1986 - "No significant difference was observed regarding the thermal stability of the enzyme among normal subjects and Werner's syndrome patients. " 01/01/1980 - "Short communication lysosomal and mitochondrial heat labile enzymes in Werner's syndrome fibroblasts." 05/08/1975 - "Heat-labile enzymes in Werner's syndrome fibroblasts."
3.	VX-745IBA 09/01/2010 - "This method delivers the p38 inhibitor VX-745 in sufficient quantities for preclinical studies to rescue the aging phenotype in Werner syndrome." 09/01/2010 - "Gram-scale synthesis of the p38α MAPK-inhibitor VX-745 for preclinical studies into Werner syndrome." 11/06/2009 - "The inhibitory activity of VX-745 against p38alpha MAPK is confirmed in Werner syndrome dermal fibroblasts at 1.0 microM concentration by immunoblot assay." 09/01/2010 - "The ATP-competitive p38α MAPK inhibitor VX-745 exhibits an exquisite kinase selectivity profile, is effective in blocking p38 stress signaling in Werner syndrome dermal fibroblasts, has efficacy in clinical trials and may have therapeutic value against Werner syndrome. " 06/04/2010 - "A number of different p38 MAPK inhibitor chemotypes have been prepared rapidly and efficiently using microwave heating techniques for biological study in Werner syndrome cells, including SB203580, VX-745, RO3201195, UR-13756 and BIRB 796, and their selectivity and potency evaluated in this cellular context. "
4.	Phosphotransferases (Kinase)IBA 12/08/2011 - "Investigating the role of c-Jun N-terminal kinases in the proliferation of Werner syndrome fibroblasts using diaminopyridine inhibitors." 12/08/2011 - " Fibroblasts derived from the progeroid Werner syndrome show reduced replicative lifespan and a "stressed" morphology, both alleviated using the MAP kinase inhibitor SB203580. " 06/01/2010 - "The accelerated aging of Werner syndrome (WS) fibroblasts can be prevented by treatment with the p38 kinase inhibitor SB203580. " 09/01/2003 - "The Werner syndrome protein (WRN) is a caretaker of the human genome, and the Abl kinase is a regulator of the DNA damage response. " 03/01/1988 - "To assess the abnormalities of insulin receptor in patients with Werner's syndrome, we established Epstein-Barr virus transformed lymphocytes and studied the binding as well as kinase activities of insulin receptor. "
5.	Adenosine Triphosphate (ATP)IBA 04/30/1999 - "Here we show that human Werner syndrome DNA helicase (WRN), a member of the RecQ family of helicases, efficiently unwinds G'2 bimolecular tetraplex structures of d(CGG)7. Unwinding of d(CGG)7 by WRN requires hydrolyzable ATP and Mg2+ and is proportional to the amount of added helicase and to the time of incubation. " 09/01/2010 - "The ATP-competitive p38α MAPK inhibitor VX-745 exhibits an exquisite kinase selectivity profile, is effective in blocking p38 stress signaling in Werner syndrome dermal fibroblasts, has efficacy in clinical trials and may have therapeutic value against Werner syndrome. " 04/01/2004 - "Werner syndrome protein directly binds to the AAA ATPase p97/VCP in an ATP-dependent fashion." 01/01/2017 - "Focusing on the ATP-dependent RecQ-type DNA helicase, an enzyme involved in repair of double strand DNA, a mouse model of Werner syndrome (WS) had been proposed as a model of accelerated aging. " 12/17/2004 - "Werner syndrome patients are deficient in the Werner protein (WRN), which is a multifunctional nuclear protein possessing 3'-5' exonuclease and ATP-dependent helicase activities. "
6.	Hypoglycemic Agents (Hypoglycemics)IBA 02/01/2021 - "New antidiabetic drugs, such as dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists, could be potentially beneficial for patients with Werner syndrome. " 02/01/1988 - "Diabetes mellitus associated with Werner's syndrome is generally mild with high immunoreactive insulin value and is controllable by diet therapy and oral antidiabetic drugs. " 07/01/1994 - "In the present study, CS-045((+/-)-5-[4-(6-Hydroxy-2,5,7,8-tetramethylchroman-2-ylmet hoxy)benzyl] - 2,4-thiazolidinedione, a new oral hypoglycemic agent which reportedly reduces insulin resistance, was administered to 2 Werner's syndrome patients. "
7.	Troglitazone (Rezulin)FDA Link 08/01/1997 - "Troglitazone ameliorates insulin resistance in patients with Werner's syndrome." 05/01/1998 - "Patients with impaired glucose tolerance, syndrome X, polycystic ovary syndrome, gestational diabetes, or Werner's syndrome may also benefit from troglitazone. " 07/01/1994 - "Increased insulin responsiveness after CS-045 treatment in diabetes associated with Werner's syndrome." 07/01/1994 - "In the present study, CS-045((+/-)-5-[4-(6-Hydroxy-2,5,7,8-tetramethylchroman-2-ylmet hoxy)benzyl] - 2,4-thiazolidinedione, a new oral hypoglycemic agent which reportedly reduces insulin resistance, was administered to 2 Werner's syndrome patients. "
8.	2,4-thiazolidinedione (thiazolidinedione)IBA 01/01/2010 - "Biguanide, but not thiazolidinedione, improved insulin resistance in Werner syndrome." 07/01/1994 - "In the present study, CS-045((+/-)-5-[4-(6-Hydroxy-2,5,7,8-tetramethylchroman-2-ylmet hoxy)benzyl] - 2,4-thiazolidinedione, a new oral hypoglycemic agent which reportedly reduces insulin resistance, was administered to 2 Werner's syndrome patients. "
9.	RNA (Ribonucleic Acid)IBA 11/23/2001 - "This result supports the idea that imperfect messages containing premature termination codons are eliminated by the RNA surveillance system, suggesting the significance of the NMD mechanism in the etiology of Werner syndrome." 02/01/1990 - "Increased collagen synthesis accompanying elevated m-RNA levels in cultured Werner's syndrome fibroblasts." 01/01/2006 - "Werner syndrome, caused by the homologous mutation of RecQ3 RNA/DNA helicase (WRN), is often misdiagnosed as systemic sclerosis (SSc) because of apparent similar skin changes and its relatively high frequency in Japan. " 08/01/1992 - "Each mRNA was analyzed using total RNA preparations isolated from normal fibroblast cultures at different phases of the in vitro life span and from cultures derived from donors with the premature senescence syndromes characterized as Werner syndrome, progeria (Hutchinson-Gilford) syndrome, or Cockayne syndrome. "
10.	Oxygen (Dioxygen)IBA 04/01/1995 - "HDF from a subject with Werner syndrome, a premature aging disease, which are known to have reduced replicative potential in vitro, also showed 43% increase in life span under the lowest oxygen conditions. " 01/01/1981 - "Effects of radical-scavenging enzymes and reduced oxygen exposure on growth and chromosome abnormalities of Werner syndrome cultured skin fibroblasts." 01/01/1981 - "All cultures (untreated, treated with enzymes, treated with reduced oxygen exposure) displayed the limited in vitro growth potential and cytogenetic abnormality characteristic of Werner's syndrome FL cells; thus the underlying defect in Werner's syndrome does not appear to be related to defective protection against or repair of damage by free radicals." 07/01/1981 - "We prepared erythrocytes and lymphocytes from three patients with Werner's syndrome and determined four important enzymes protecting against oxygen toxicity; CuZn superoxide dismutase, Mn superoxide dismutase, catalase and glutathione peroxidase. "

Therapies and Procedures

1.	Glycemic Control 12/01/2012 - "Sitagliptin successfully ameliorates glycemic control in Werner syndrome with diabetes." 03/01/2016 - "Improved Glycemic Control and Vascular Function and Reduction of Abdominal Fat Accumulation with Liraglutide in a Case of Werner Syndrome with Diabetes Mellitus."
2.	Penetrating Keratoplasty 06/01/1993 - "Although penetrating keratoplasty appears to be the best treatment for bullous keratopathy, there have been few reports on bullous keratopathy in patients with Werner's syndrome. " 06/01/1993 - "In both cases, visual acuity was improved, suggesting that penetrating keratoplasty is a recommendable treatment for bullous keratopathy in patients with Werner's syndrome." 06/01/1993 - "Here we report two patients with Werner's syndrome who underwent penetrating keratoplasty for the treatment of bullous keratopathy. " 06/01/1993 - "[Two cases of Werner's syndrome treated with penetrating keratoplasty]."
3.	Lasers (Laser) 03/12/2014 - "Patients with Werner syndrome can develop severe CME after laser treatment. " 11/01/2012 - "Endothelial cell study in a case of Werner's syndrome undergoing phacoemulsification and Yettrium-Aluminum-Garnet laser capsulotomy." 01/01/2017 - "Here we show that RECQL5 associates longer at laser-induced DNA double-strand breaks in the absence of Werner syndrome (WRN) protein, and that it interacts physically and functionally with WRN both in vivo and in vitro. " 01/01/2013 - "Here we show that RECQL5 associates longer at laser-induced DNA double-strand breaks in the absence of Werner syndrome (WRN) protein, and that it interacts physically and functionally with WRN both in vivo and in vitro. "
4.	Aftercare (After-Treatment) 01/01/2002 - "[Chromosomal abnormalities in lymphocytes from a patient with Werner's syndrome in intact culture and after treatment with halogenated analogs of thymidine]." 04/17/2009 - "In this study, we examined the changes of telomerase and Werner's syndrome RecQ (WRN) helicase after treatment with 2DG, because of the involvement of recQ helicase in the regulation of telomeres. " 10/15/2006 - "RECQL4 localization did not change after treatment with the DNA-damaging agents bleomycin, etoposide, UV irradiation and gamma irradiation, in contrast to the Bloom and Werner syndrome helicases that relocate to distinct nuclear foci after damage. "
5.	Caloric Restriction 03/01/2020 - "To further establish whether our data correlated with gene expression alterations associated with aging and senescence, we compared our global transcriptional data with additional published datasets, including alterations in gene expression in the neocortex and cerebellum of old mice, human frontal cortex after age of 40, gene alterations in the Werner syndrome, rodent caloric restriction, Ras and oncogene-induced senescence in fibroblasts, and to tissues besides the brain such as the muscle and kidney. " 12/01/2008 - "Clinical trials including caloric restriction, sirtuin activators, and p38 MAPK inhibitors against both pathological aging such as metabolic syndrome, diabetes mellitus, rheumatoid arthritis, and Werner syndrome and physiological aging have been proposed."