title: Hyperhomocysteinemia as a risk factor for the neuronal system disorders.
abstract: Elevated concentration of the homocysteine (Hcy) in human tissues, resulting either from mutations in genes enconding Hcy-metabolizing enzymes, or from deficiences of folic acid has recognized cytotoxic effect. Even a mild Hcy level increase is a risk factor for cardiovascular diseases and stroke in humans and also a risk factor for neurodegenerative disordes, such as dementia, or Alzheimer's disease. However, it is not yet clear whether homocysteine is a marker, or a causative agent. We present here an overview of recent data on the homocysteine metabolism and on the genetic and the metabolic causes of hyperhomocysteinemia-related pathologies in humans. In context of our results which detected an increased oxidative stress in hyperhomocysteinemic rats we discuss here the role of free radicals in this disorder. Imbalance between homocysteine auto-oxidation, production of reactive metabolites and cellular antioxidant defence induced by hyperhomocysteinemia results to cytotoxicity by oxidizing membrane lipids and proteins. Consequently, protein thiolation and homocysteinylation results in the structural and functional modifications of cells, including neuronal ones. It is our hope that identification of prophylacting factors effective in the prevention of toxic effect of Hcy would lead to improved therapeutics, especially the brain tissue.
authors.affiliation: Department of Medical Biochemistry, Comenius University in Bratislava, Jessenius Faculty of Medicine, Martin, Slovakia. drgova@jfmed.uniba.sk.
authors.forename: M
authors.initials: M
authors.lastname: Petras
authors.forename: Z
authors.initials: Z
authors.lastname: Tatarkova
authors.forename: M
authors.initials: M
authors.lastname: Kovalska
authors.forename: D
authors.initials: D
authors.lastname: Mokra
authors.forename: D
authors.initials: D
authors.lastname: Dobrota
authors.forename: J
authors.initials: J
authors.lastname: Lehotsky
authors.forename: A
authors.initials: A
authors.lastname: Drgova
mesh_terms: D000818:Animals; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D012307:Risk Factors
chemical_list: D006710:Homocysteine