title: Why is homocysteine toxic for the nervous and immune systems?
abstract: Hyperhomocysteinemia is a risk factor for a number of neurodegenerative and cardiovascular diseases. We have shown that homocysteine induces excitotoxic effects in cells expressing glutamate receptors of the NMDA class. These receptors were found not only in neurons but also in immune-competent cells, neutrophils, red blood cells, cardiomyocytes, and osteoblasts. Activation of these cells by homocysteine results in an increase in cytoplasmic calcium ions, accumulation of reactive oxygen species, and activation of MAP kinase. An overload of immune-competent cells activates both necrotic and apoptotic cell death, whereas the neuropeptide carnosine (an antioxidant and immune modulator) protects cells against both processes. In a model of prenatal hyperhomocysteinemia in rats, we have found that carnosine protects animals against homocysteine toxicity with no change of the blood homocysteine levels. The efficiency of carnosine has also been demonstrated in clinical trials of chronic brain ischemia and Parkinson's disease.
authors.affiliation: Department of Biochemistry and International Biotechnological Center, M.V. Lomonosov Moscow State University, Moscow, Russia. aaboldyrev@mail.ru
authors.forename: Alexander
authors.initials: A
authors.lastname: Boldyrev
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Bryushkova
authors.forename: Anna
authors.initials: A
authors.lastname: Mashkina
authors.forename: Elizaveta
authors.initials: E
authors.lastname: Vladychenskaya
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D002336:Carnosine / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006710:Homocysteine / Q000031:analogs & derivatives / Q000097:blood* / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications; D015213:Neuroimmunomodulation / Q000187:drug effects* / Q000502:physiology*; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D011247:Pregnancy; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D006710:Homocysteine; C007956:homocysteic acid; D002336:Carnosine