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: 567 relevant articles (11 outcomes, 35 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Insulin Resistance
2.	Neoplasms (Cancer)
3.	Chromosome Aberrations (Chromosome Abnormalities)
4.	Progeria (Hutchinson Gilford Syndrome)
5.	Atherosclerosis

Experts

1.	Bohr, Vilhelm A: 34 articles (01/2014 - 08/2002)
2.	Lebel, Michel: 16 articles (12/2015 - 01/2002)
3.	Kipling, David: 16 articles (01/2015 - 04/2003)
4.	Davis, Terence: 16 articles (01/2015 - 04/2003)
5.	Opresko, Patricia L: 15 articles (11/2011 - 06/2003)
6.	Brosh, Robert M: 12 articles (10/2013 - 06/2002)
7.	Yokote, Koutaro: 11 articles (06/2015 - 09/2004)
8.	Bagley, Mark C: 11 articles (01/2015 - 11/2006)
9.	Goto, Makoto: 11 articles (12/2014 - 03/2003)
10.	Enomoto, Takemi: 11 articles (09/2014 - 08/2002)

Drugs and Biologics

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

1.	DNA (Deoxyribonucleic Acid)IBA 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]." 08/01/2014 - "Acetylation of Werner syndrome protein (WRN): relationships with DNA damage, DNA replication and DNA metabolic activities." 07/01/2014 - "Strand exchange of telomeric DNA catalyzed by the Werner syndrome protein (WRN) is specifically stimulated by TRF2." 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. "
2.	EnzymesIBA 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." 07/01/1980 - "Thermolabile enzymes in progeria and Werner syndrome: evidence contrary to the protein error hypothesis." 01/01/1977 - "Chromosome breaks in Werner's syndrome and their prevention in vitro by radical-scavenging enzymes." 02/02/2001 - "In addition to their activity in unwinding duplex substrates, recent studies show that the two enzymes are able to unwind G2 and G4 tetraplexes, prompting speculation that failure to resolve these structures in Bloom syndrome and Werner syndrome cells may contribute to genome instability. "
3.	Phosphotransferases (Kinase)IBA 01/01/2011 - "Investigating the role of c-Jun N-terminal kinases in the proliferation of Werner syndrome fibroblasts using diaminopyridine inhibitors." 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. " 01/01/2011 - " 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. " 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. "
4.	Adenosine Triphosphate (ATP)IBA 04/01/2004 - "Werner syndrome protein directly binds to the AAA ATPase p97/VCP in an ATP-dependent fashion." 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. " 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. " 05/27/1997 - "These predictions include an ATP-binding domain in the product of hereditary nonpolyposis colon cancer gene (a MutL homolog), which is conserved in the HS90 family of chaperone proteins, type II DNA topoisomerases, and histidine kinases, and a nuclease domain homologous to bacterial RNase D and the 3'-5' exonuclease domain of DNA polymerase I in the Werner syndrome gene product."
5.	troglitazone (Rezulin)FDA Link 08/01/1997 - "Troglitazone ameliorates insulin resistance in patients with Werner's syndrome." 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. " 05/01/1998 - "Patients with impaired glucose tolerance, syndrome X, polycystic ovary syndrome, gestational diabetes, or Werner's syndrome may also benefit from troglitazone. "
6.	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. "
7.	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. "
8.	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. " 06/01/1999 - "Werner syndrome helicase contains a 5'-->3' exonuclease activity that digests DNA and RNA strands in DNA/DNA and RNA/DNA duplexes dependent on unwinding."
9.	OxygenIBA 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. "
10.	Nonsense Codon (Nonsense Mutation)IBA 01/01/2015 - "A novel Werner Syndrome mutation: pharmacological treatment by read-through of nonsense mutations and epigenetic therapies." 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."

Therapies and Procedures

1.	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]."
2.	Aftercare (After-Treatment) 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. " 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]." 09/15/2000 - "After treatment with Werner DNA helicase the TRDC dissociated into smaller fragments, provided that human replication protein A was present, indicating that: (i) the TRDC is a new substrate for the Werner syndrome helicase; (ii) the telomere repeat sequence re-anneals rapidly unless unwound single-stranded regions are protected by replication protein A; (iii) the TRDC may provide a new clue to understanding deleterious telomere-totelomere interactions that can lead to genomic instability. " 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. "
3.	Lasers (Laser) 01/01/2014 - "Patients with Werner syndrome can develop severe CME after laser treatment. " 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. " 11/01/2012 - "Endothelial cell study in a case of Werner's syndrome undergoing phacoemulsification and Yettrium-Aluminum-Garnet laser capsulotomy."
4.	Phacoemulsification 12/01/2000 - "This experience with these two patients showed that Werner's syndrome cataracts can be safely managed with the current phacoemulsification and small-incision surgery techniques." 12/01/2000 - "[Cataract surgery by phacoemulsification in Werner's syndrome]." 11/01/2012 - "Endothelial cell study in a case of Werner's syndrome undergoing phacoemulsification and Yettrium-Aluminum-Garnet laser capsulotomy."
5.	Caloric Restriction 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."