Lathyrism: Evidence for Role of the Neuroexcitatory Aminoacid Boaa

Spencer, Peter S.; Ludolph, Albert C.; Dwivedi, M. P.; Roy, Dwijendra N.; Hugon, Jacques; Schaumburg, Herbert H.

doi:10.1016/s0140-6736(86)90468-x

Cited by 358 publications

(122 citation statements)

References 6 publications

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“…In humans, spinal motoneurons selectively die from the suspected AMPA agonist ␤-N-oxalylamino-L-alanine (lathyrism) (20). Remarkably, the expression of functionally altered AMPA channels by impaired Q͞R site editing of GluR-B leads in mice to severe seizures and premature death during the first postnatal month (6), precluding the likely development of motoneuron disease in later life.…”

Section: Discussionmentioning

confidence: 99%

“…The genetic mechanisms controlling GluR-B subunit expression and the extent of Q͞R site editing in motoneurons may, if faulty, trigger the phenotype of motoneuron disease by itself, on the background of facilitating environmental factors (lathyrism) (20), excessive exercise, such as in high-performance professional athletes (23), or combinations of both. Similar molecular mechanisms may apply to the loss of neurons in the amygdala and hypothalamus in GluR-B(N) mice and ALS patients, resulting in the phenotype of affective lability or low weight frequently also noted in humans afflicted with ALS (24).…”

Section: Discussionmentioning

confidence: 99%

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Late-onset motoneuron disease caused by a functionally modified AMPA receptor subunit

Kuner

Groom²,

Bresink³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Amyotrophic lateral sclerosis (ALS) is a devastating disorder of the central nervous system in middle and old age that leads to progressive loss of spinal motoneurons. Transgenic mice overexpressing mutated human Cu 2؉ ͞Zn 2؉ superoxide dismutase 1 (SOD1) reproduce clinical features of the familial form of ALS. However, changes in SOD1 activity do not correlate with severity of motor decline in sporadic cases, indicating that targets unrelated to superoxide metabolism contribute to the pathogenesis of the disease. We show here that transgenic expression in mice of GluR-B(N)-containing L-␣-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA) receptors with increased Ca 2؉ permeability leads to late-onset degeneration of neurons in the spinal cord and decline of motor functions. Neuronal death progresses over the entire lifespan but manifests clinically in late adulthood, resembling the course of a slow neurodegenerative disorder. Additional transgenic expression of mutated human SOD1 accelerates disease progression, aggravates the severity of motor decline, and decreases survival. These observations link persistently elevated Ca 2؉ influx through AMPA channels with progressive motor decline and late-onset degeneration of spinal motoneurons, indicating that functionally altered AMPA channels may be causally related to pathogenesis of sporadic ALS in humans.amyotrophic lateral sclerosis ͉ Ca 2ϩ permeable ion channels ͉ GluR-B gene

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Late-onset motoneuron disease caused by a functionally modified AMPA receptor subunit

Kuner

Groom²,

Bresink³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…Both compounds initiate a slowly developing toxic process at high concentrations. In humans, signs of neurolathyrism appear after eating Lathyrus sativus seeds for~2 months; however, in monkeys, a BOAAenriched diet caused signs of this condition after just 2-4 weeks (Spencer et al, 1986). Although the type of neuronal exposure examined in this study is not as prolonged as this, a recent mathematical analysis applied to survival data of neuronal cells after BOAA exposure found that even very low doses of BOAA could induce a detectable toxicity that would lead eventually to complete cell death (La Bella et al, 1996).…”

Section: Figmentioning

confidence: 99%

The Dietary Excitotoxins β‐N‐Methylamino‐l‐Alanine and β‐N‐Oxalylamino‐l‐Alanine Induce Necrotic‐ and Apoptotic‐Like Death of Rat Cerebellar Granule Cells

Staton

Bristow

1997

Journal of Neurochemistry

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Abstract:The neurotoxic properties of the dietary excitotoxins /3-N-methylamino-L-alanine and~3-N-oxalylamino-L-alanine have been studied in rat cerebellar granule cells and compared with those of glutamate. Glutamate caused dose-dependent death of cerebellar granule cells after a 30-min exposure when viability was assessed 24 h later. ß-N-Methylamino-L-alanine and /3-N-oxalylamino-L-alanine, however, were toxic only after 24 or 48 h of exposure. The neurotoxic effects of ß-N-methylaminO-L-alanine were blocked by D(-)-2-amino-5-phosphonopentanoic acid, and those of ß-N-oxalylamino-Lalanine were blocked by kynurenic acid, which demonstrated that these excitotoxins caused cerebellar granule cell death through the activation of glutamate receptors.

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“…Lathyrus sativus, a protein rich hardy legume that grows under extreme environmental conditions, is not edible due to the presence of a neurotoxin ␤-N-oxalyl-L-␣,␤-diaminopropionic acid. Oxalic acid is an essential precursor of the neurotoxin (6). ␤-N-Oxalyl-L-␣,␤-diaminopropionic acid acts as a metabolic antagonist of glutamic acid, which is involved in the transmission of nerve impulse in the brain (7).…”

mentioning

confidence: 99%

Oxalate Decarboxylase from Collybia velutipes

Kesarwani

Azam

Natarajan

et al. 2000

Journal of Biological Chemistry

115

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Oxalic acid is present as nutritional stress in many crop plants like Amaranth and Lathyrus. Oxalic acid has also been found to be involved in the attacking mechanism of several phytopathogenic fungi. A full-length cDNA for oxalate decarboxylase, an oxalate-catabolizing enzyme, was isolated by using 5-rapid amplification of cDNA ends-polymerase chain reaction of a partial cDNA as cloned earlier from our laboratory (

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Lathyrism: Evidence for Role of the Neuroexcitatory Aminoacid Boaa

Cited by 358 publications

References 6 publications

Late-onset motoneuron disease caused by a functionally modified AMPA receptor subunit

Late-onset motoneuron disease caused by a functionally modified AMPA receptor subunit

The Dietary Excitotoxins β‐N‐Methylamino‐l‐Alanine and β‐N‐Oxalylamino‐l‐Alanine Induce Necrotic‐ and Apoptotic‐Like Death of Rat Cerebellar Granule Cells

Oxalate Decarboxylase from Collybia velutipes

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