TY - JOUR
T1 - Food toxins, AMPA receptors, and motor neuron diseases
AU - Spencer, Peter S.
N1 - Funding Information:
I thank the University of Arkansas for Medical Sciences for the honor bestowed on me in recognizing these collaborative research contributions acknowledged on page 563 and by text citation, and the Snider Foundation for their support of toxicological science. I am indebted to Dr. Donald McMillan and Dr. Jack Hinson and their associates for making this conference possible.
Funding Information:
This research was supported principally by NIH grant NS 19611 and the Third World Medical Research Foundation.
PY - 1999
Y1 - 1999
N2 - Environmental chemicals involved in the etiology of human neurodegenerative disorders are challenging to identify. Described here is research designed to determine the etiology and molecular pathogenesis of nerve cell degeneration in two little known corticomotoneuronal diseases with established environmental triggers. Both conditions are toxic-nutritional disorders dominated by persistent spastic weakness of the legs and degeneration of corresponding corticospinal pathways. Lathyrism, a disease caused by dietary dependence on grass pea (Lathyrus sativus), is mediated by a stereospecific plant amino acid (β-N-oxalylamino-L-alanine) that serves as a potent agonist at the (RS)-α-amino-3-hydroxy-5-methyl-isoxazole-4- propionic acid (AMPA) subclass of neuronal glutamate receptors. A neurologically similar disorder, konzo ('tied legs'), is found among protein- poor African communities that rely for food on cyanogen-containing cassava roots. Thiocyanate, the principal metabolite of cyanide, is an attractive etiologic candidate for konzo because it selectively promotes the action of glutamate at AMPA receptors. Studies are urgently needed to assess the health effects of cassava and other cyanogenic plants, components of which are widely used as food.
AB - Environmental chemicals involved in the etiology of human neurodegenerative disorders are challenging to identify. Described here is research designed to determine the etiology and molecular pathogenesis of nerve cell degeneration in two little known corticomotoneuronal diseases with established environmental triggers. Both conditions are toxic-nutritional disorders dominated by persistent spastic weakness of the legs and degeneration of corresponding corticospinal pathways. Lathyrism, a disease caused by dietary dependence on grass pea (Lathyrus sativus), is mediated by a stereospecific plant amino acid (β-N-oxalylamino-L-alanine) that serves as a potent agonist at the (RS)-α-amino-3-hydroxy-5-methyl-isoxazole-4- propionic acid (AMPA) subclass of neuronal glutamate receptors. A neurologically similar disorder, konzo ('tied legs'), is found among protein- poor African communities that rely for food on cyanogen-containing cassava roots. Thiocyanate, the principal metabolite of cyanide, is an attractive etiologic candidate for konzo because it selectively promotes the action of glutamate at AMPA receptors. Studies are urgently needed to assess the health effects of cassava and other cyanogenic plants, components of which are widely used as food.
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U2 - 10.1081/DMR-100101936
DO - 10.1081/DMR-100101936
M3 - Article
C2 - 10461541
AN - SCOPUS:0032786968
SN - 0360-2532
VL - 31
SP - 561
EP - 587
JO - Drug Metabolism Reviews
JF - Drug Metabolism Reviews
IS - 3
ER -