)| PMID |
16764863 ( ) |
|---|---|
| Title | BMAA selectively injures motor neurons via AMPA/kainate receptor activation. |
| Abstract | The toxin beta-methylamino-l-alanine (BMAA) has been proposed to contribute to amyotrophic lateral sclerosis-Parkinsonism Dementia Complex of Guam (ALS/PDC) based on its ability to induce a similar disease phenotype in primates and its presence in cycad seeds, which constituted a dietary item in afflicted populations. Concerns about the apparent low potency of this toxin in relation to estimated levels of human ingestion led to a slowing of BMAA research. However, recent reports identifying potential new routes of exposure compel a re-examination of the BMAA/cycad hypothesis. BMAA was found to induce selective motor neuron (MN) loss in dissociated mixed spinal cord cultures at concentrations ( approximately 30 muM) significantly lower than those previously found to induce widespread neuronal degeneration. The glutamate receptor antagonist NBQX prevented BMAA-induced death, implicating excitotoxic activation of AMPA/kainate receptors. Using microfluorimetric techniques, we further found that BMAA induced preferential [Ca(2+)](i) rises and selective reactive oxygen species (ROS) generation in MNs with minimal effect on other spinal neurons. Cycad seed extracts also triggered preferential AMPA/kainate-receptor-dependent MN injury, consistent with the idea that BMAA is a crucial toxic component in this plant. Present findings support the hypothesis that BMAA may contribute to the selective MN loss in ALS/PDC. University of California, Irvine, Irvine, CA 92697-4292, USA. |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 4571 | GRIA1 | glutamate receptor, ionotropic, AMPA 1 | 4 | glutamate receptor | |
| 2898 | DLD | dihydrolipoamide dehydrogenase | 2 | diaphorase | |
| 30000 | BBS9 | Bardet-Biedl syndrome 9 | 1 | C18 | |
| 3229 | EGF | epidermal growth factor (beta-urogastrone) | 1 | EGF-treated | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 30000 | BBS9 | Bardet-Biedl syndrome 9 | C18 | 0.3 | Injector Waters 1525 Binary Solvent Delivery System and Waters Nova-Pak C18 column 300_amp_#xa0 mm_amp_#xa0 _amp_#xd7 _amp_#xa0 3.9_amp_#xa0 mm at 37_amp_#xb0 C |
| 3229 | EGF | epidermal growth factor (beta-urogastrone) | EGF-treated | 0.3 | Cells were plated on a previously established layer of EGF-treated astrocytes grown on either 15_amp_#xa0 mm Primaria-coated culture plates (Falcon, |
| 4571 | GRIA1 | glutamate receptor, ionotropic, AMPA 1 | glutamate receptor | 1.0 | to further examine the mechanisms of bmaa induced injury to mns cultures were exposed to bmaa 100_amp_#xa0;_amp_#x3bc;m in the presence of the selective glutamate receptor antagonists mk 801 10_amp_#xa0;_amp_#x3bc;m and/or nbqx 10_amp_#xa0;_amp_#x3bc;m fig 1 c . |
| 4571 | GRIA1 | glutamate receptor, ionotropic, AMPA 1 | glutamate receptor | 1.0 | fluorescence imaging techniques were used to address mechanisms of mn injury downstream from glutamate receptor activation. |
| 4571 | GRIA1 | glutamate receptor, ionotropic, AMPA 1 | glutamate receptor | 1.0 | previous studies have demonstrated that glutamate receptor mediated ca 2+ entry triggers the generation of ros lafon cazal et al. 1993 dugan et al. 1995 reynolds and hastings 1995 carriedo et al. 1998 and carriedo et al. 2000 . |
| 4571 | GRIA1 | glutamate receptor, ionotropic, AMPA 1 | glutamate receptor | 1.0 | enotypic development eagleson et al. 1985 schaffner et al. 1987 and martinou et al. 1989 and results in mns far more closely resembling mns in vivo in terms of such factors as axodendritic growth and glutamate receptor expression than occurs in pure mn cultures vandenberghe et al. 1998 . |
| 2898 | DLD | dihydrolipoamide dehydrogenase | diaphorase | 1.0 | in a previous study we identified a subpopulation of cortical neurons nadph diaphorase neurons which was far more susceptible to bmaa injury than the overall cortical neuronal population weiss et al. 1989a and weiss et al. 1989b providing precedent for the idea that vulnerability to bm |
| 2898 | DLD | dihydrolipoamide dehydrogenase | diaphorase | 1.0 | however in our prior studies we found that the preferential injury to the nadph diaphorase neurons induced by lower bmaa exposures was predominantly mediated by ampa/kainate receptors weiss et al. 1989a weiss et al. 1989b and smith and meldrum 1990 . |