Neurolathyrism: mitochondrial dysfunction in excitotoxicity mediated by L-beta-oxalyl aminoalanine.
beta-N-Oxalyl amino-L-alanine (L-BOAA); synonym beta-N-oxalyl-alpha,beta-diaminopropionic acid (beta-ODAP) is a naturally occurring non-protein amino acid present in the chickling pea from the plant Lathyrus sativus grown in drought prone areas. Ingestion of L-BOAA as a staple diet results in a progressive neurodegenerative condition, neurolathyrism, a form of motor neuron disease which affects the upper motor neurons and anterior horn cells of the lumbar spinal cord. L-BOAA is an excitatory acid and acts as an agonist at the AMPA receptor. One of the primary effects of L-BOAA toxicity is the inhibition of mitochondrial complex I selectively in the motor cortex and lumbar spinal cord. Recent evidence has suggested that the mitochondrial dysfunction is a consequence of oxidation protein thiol groups as a result of generation of reactive oxygen species. Mitochondrial complex I is highly to vulnerable to inactivation through oxidation of vital sulfhydryl groups. Thiol antioxidants such as alpha-liopic acid offer a method of protecting mitochondrial function. A common mechanism involving oxidation of protein thiol groups may underlie neurodegeneration occurring through mitochondrial dysfunction induced by excitatory amino acid.
Ravindranath
Vijayalakshmi
V
National Brain Research Centre, SCO 5, 6 & 7, Sector 15, Part-II, Gurgaon, Haryana 122001, India. vijir@vsnl.com
D000599:Amino Acids, Diamino; D000818:Animals; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D018846:Excitatory Amino Acids / Q000633:toxicity*; D006801:Humans; D007842:Lathyrism / Q000139:chemically induced / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000633:toxicity*
D000599:Amino Acids, Diamino; D018846:Excitatory Amino Acids; D017470:Receptors, Glutamate; D015091:beta-Alanine; C100126:oxalyldiaminopropionic acid; D002118:Calcium