title: Role of glutamate and nitric oxide in onset of motor neuron degeneration in neurolathyrism.
abstract: Neurolathyrism is associated with a complex pattern of alterations in the glutamatergic system of the cortical motor region of brain. It is a neurological disorder consorted with excessive consumption of Lathyrus sativus (Grass pea), comprising large amounts of the neurotoxin, β-N-oxalyl-L-α,β-diaminopropionic acid (ODAP). ODAP being a potent agonist of ionotropic glutamate receptors enhances their activity and also blocks the astrocytic glutamate/cystine transporters, abutting the neurons. This leads to the sustained increase in the concentration of Glutamate in the synapse which triggers excitotoxicity. L. sativus also contains high levels of arginine and homoarginine which are natural substrates of nitric oxide production, when NO levels increases, it forms peroxynitrite radicals which cause irreparable damage to mitochondria and cellular macromolecules leading to motor neuron degeneration. This review brings together all the molecular events reported so far, emphasizing on the possible role of glutamate and nitric oxide mediated cell death.
authors.affiliation: Food and Drug Toxicology Research Center, National Institute of Nutrition, Hyderabad 500007, India. alkhandare@yahoo.com
authors.forename: Arjun L
authors.initials: AL
authors.lastname: Khandare
authors.forename: M
authors.initials: M
authors.lastname: Ankulu
authors.forename: N
authors.initials: N
authors.lastname: Aparna
mesh_terms: D000818:Animals; D004967:Estrogens / Q000378:metabolism; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007842:Lathyrism / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism; D009044:Motor Cortex / Q000378:metabolism* / Q000473:pathology; D016472:Motor Neuron Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration; D009569:Nitric Oxide / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D004967:Estrogens; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D018698:Glutamic Acid; D005721:Glutamate-Cysteine Ligase