title: Homocystinuria: Therapeutic approach.
abstract: Homocystinuria is a disorder of sulfur metabolism pathway caused by deficiency of cystathionine β-synthase (CBS). It is characterized by increased accumulation of homocysteine (Hcy) in the cells and plasma. Increased homocysteine results in various vascular and neurological complications. Present strategies to lower cellular and plasma homocysteine levels include vitamin B6 intake, dietary methionine restriction, betaine supplementation, folate and vitamin B12 administration. However, these strategies are inefficient for treatment of homocystinuria. In recent years, advances have been made towards developing new strategies to treat homocystinuria. These mainly include functional restoration to mutant CBS, enhanced clearance of Hcy from the body, prevention of N-homocysteinylation-induced toxicity and inhibition of homocysteine-induced oxidative stress. In this review, we have exclusively discussed the recent advances that have been achieved towards the treatment of homocystinuria. The review is an attempt to help clinicians in developing effective therapeutic strategies and designing novel drugs against homocystinuria.
authors.affiliation: Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110 007, India.
authors.forename: Tarun
authors.initials: T
authors.lastname: Kumar
authors.affiliation: Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110 007, India.
authors.forename: Gurumayum Suraj
authors.initials: GS
authors.lastname: Sharma
authors.affiliation: Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110 007, India. Electronic address: lairksingh@gmail.com.
authors.forename: Laishram Rajendrakumar
authors.initials: LR
authors.lastname: Singh
mesh_terms: D001622:Betaine / Q000008:administration & dosage / Q000627:therapeutic use*; D003541:Cystathionine beta-Synthase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D006712:Homocystinuria / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018384:Oxidative Stress / Q000187:drug effects; D054852:Small Molecule Libraries / Q000494:pharmacology; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000627:therapeutic use*; D025101:Vitamin B 6 / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D054852:Small Molecule Libraries; D001622:Betaine; D025101:Vitamin B 6; D003541:Cystathionine beta-Synthase; D014805:Vitamin B 12
keywords: Cystathionine β-synthase; Dietary treatment of homocystinuria; Homocysteine toxicity; Homocystinuria; New therapeutic strategies; Protein homocysteinylation