Rabbit Anti-Human Cleaved-Lamin A (D230) (a.a. 181-230) Polyclonal antibody

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic condition associated with mutations in the LMNA gene. This disease recapitulates some aspects of normal aging, such as hair loss, thin skin, joint stiffness, and atherosclerosis. The latter leads to heart attack or stroke that causes death at an average age of 14.6 years in children with HGPS. The typical LMNA mutation results in the production of a truncated prelamin A protein, progerin, that remains permanently farnesylated and abnormally associated with the nuclear envelope. Farnesyltransferase inhibitors (FTIs) reverse nuclear structure abnormalities that are characteristic of HGPS cells. The first clinical trial using the FTI, Ionafarnib, demonstrated some improvements in HGPS children and, in particular, showed a decrease in arterial stiffness. Recently, we reported that sulforaphane, an antioxidant derived from cruciferous vegetables, efficiently stimulates autophagy and enhances progerin clearance in HGPS fibroblasts. In the present study, we investigated the effect of combined lonafarnib and sulforaphane treartment in HGPS fibroblast cultures. We report that co-administration of both drugs exerts a synergistic and additive positive effect on autophagy activity but was cytotoxic to HGPS cells. In contrast, intermittent treatment with lonafarnib followed by sulforaphane separately and in repeated cycles rescued the HGPS cellular phenotype. We propose that intermittent treatment with FTI and SFN separately might be a promising therapeutic avenue for children with HGPS.

Werner syndrome (WS) is a rare, adult-onset progeroid syndrome. Classic WS is caused by WRN mutation and partial atypical WS (AWS) is caused by DINA mutation. A 19-year-old female patient with irregular menstruation and hyperglycemia was admitted. Physical examination revealed characteristic faces of progeria, graying and thinning of the hair scalp. thinner and atrophic skin over the hands and feet, as well as lipoatrophy of the extremities, undeveloped breasts at Tanner stage 3, and short stature. The patient also suffered from severe insulin-resistant diabetes mellitus, hyperlipidemia, fatty liver, and polycystic ovarian morphology. Possible WS was considered and both WRN and LMNA genes were analyzed. A novel missense mutation p.L140Q (c.419T>A) in the LMNA gene was identified and confirmed the diagnosis of AWS. Her father was a carrier of the same mutation. We carried out therapy for lowering blood glucose and lipid and improving insulin resistance, et al. The fasting glucose, postprandial glucose and triglyceride level was improved after treatment for 9 days. Literature review of AWS was performed to identify characteristics of the disease. Diabetes mellitus is one of the clinical manifestations of WS and attention must give to the differential diagnosis. Gene analysis is critical in the diagnosis of WS. According to the literature, classic and atypical WS differ in incidence, pathogenic gene, and clinical manifestations. Characteristic dermatological pathology may be significantly more important for the initial identification of AWS. Early detection, appropriate treatments, and regular follow-up may improve prognosis and survival of WS patients.