Homocysteine and its derivatives as possible modulators of neuronal and non-neuronal cell glutamate receptors in Alzheimer's disease.
Homocysteine (HC) and its derivatives may be involved in the etiology of Alzheimer's Disease (AD), although the precise mechanisms by which these compounds could cause cellular pathology are still unclear. Because interactions of HC with glutamate receptors have been implicated in AD, receptor-mediated effects of HC and homocysteic acid (HCA) on neurons and lymphocytes have been analyzed. Activation of glutamate receptors by these compounds has been shown to increase intracellular calcium and free radical levels in both types of cells, which may serve as a signal for development of apoptosis. Activation of group III metabotropic glutamate receptors stimulates, whereas activation of group I and group II metabotropic glutamate receptors prevent, the excitotoxic action of HC and HCA. These effects may contribute to the neuronal pathology and immunosenescence that occur in AD. It is proposed that selective agonists of metabotropic glutamate receptors that counter the effects of HC and its derivatives may be used for correction of neuronal and immune cell metabolism in vivo under the conditions of hyperhomocysteinemia, which can occur in AD.
Boldyrev
Alexander A
AA
Department of Biochemistry, M.V. Lomonosov Moscow State University, Moscow, Russia. alexander.boldyrev@gmail.com
Johnson
Peter
P
D000544:Alzheimer Disease / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D005609:Free Radicals / Q000378:metabolism; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
D005609:Free Radicals; D017382:Reactive Oxygen Species; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D006710:Homocysteine; C007956:homocysteic acid; D002118:Calcium