Excitotoxin

Glutamate receptor. agonists ( excitotoxins ) glutamate, kainate,... 

AA A1 A01.010 Cathepsin E Excitotoxin-induced neuronal cell death... 

Mechanisms of HIV-Induced Neurodegeneration Roles for Excitotoxins and N-Methyl-o-Aspartate Receptors... 

Arbogast RE, Kozlowski MR. (1988). Quantitative morphometric analysis of the neurotoxic effects of the excitotoxin, ibotenic acid, on the basal forebrain. /Veurotox/co/ogy Spring. 9(1) 39-45. 

Some plants regularly eaten by humans contain neurotoxins that pose serious health problems. On Guam, for example, the seeds of Cycas circinalis used to be an important source of carbohydrates. Seeds of Cycas rumphii were ground into flour for tortillas. However, the seeds contain jS-N-methylamino-i-alanine, a suspected excitotoxin that overstimulates and destroys nerve cells. This compound causes a parkinsonism-like disease in macaques (Spencer et al, 1987). Other toxins have been proposed to be responsible for the disease, among them cycasin, another cycad toxin (Stone, 1993). 

Jarrard LE (2002) Use of excitotoxins to lesion the hippocampus update. Hippocampus 12 405-414... 

The PA4 peptide and an excessive amount of APP have proved to be neurotoxic. The accumulation of the pA4 peptide between synapses may be responsible for neuronal dysfunction and death (Schubert et al. 1991). PA4 could also modify the N-methyl-D-aspartate (NMDA) receptor, making possible the presence of neurotoxicity via the excitotoxin and calcium pathways [Mattson et al. 1992). Drugs that interfere with these pathways or alter calcium homeostasis have a potential therapeutic role. 

Figure 7.45 The structure of the excitotoxin domoic acid showing the similarity to glutamate, the normal agonist involved in brain function.

This is a natural toxin, and poisoning results from eating contaminated shellfish. It causes gastrointestinal distress and disturbances and neurotoxicity. Domoic acid acts as an analogue of glutamate and as an excitotoxin excess excitation leading to neuronal cell death. 

Domoic acid, known as an excitotoxin, acts as an analogue of the amino acid glutamate, incorporating a similar structure. It is believed to bind at the same site on the "kainate receptor."... 

Although quinolinic acid provides an important source of nicotinamide coenzymes, in excess it is a neurotoxic excitotoxin (Chapter 30) that has been... 

K.M. Raley-Susman, K.R. Miller, J.C. Owicki and R.M. Sapolsky, Effects of excitotoxin exposure on metabolic rate of primary hippocampal cultures application of silicon microphysiometry to neurobiology, J. Neurosci., 12(3) (1992) 773-780. 

Reed L. J. and De Belleroche J. (1990). Induction of ornithine decarboxylase in cerebral cortex by excitotoxin lesion of nucleus basalis association with postsynaptic responsiveness and N-methyl-D-aspartate receptor activation. J. Neurochem. 55 780-787. 

Disorder Excitotoxin Glutamate receptor involved Reference... 

Faden A. I. and Simon R. P. (1988). A potential role for excitotoxins in the pathophysiology of spinal cord injury. Ann. Neurol. 23 623-626. 

Griffiths T., Evans M. C., and Meldrum B. S. (1983). Temporal lobe epilepsy, excitotoxins and the mechanism of selective neuronal loss. In Fuxe K., Roberts P., and Schwarcz R. (eds.), Excitotoxins. Macmillan Publ. Co. Inc., New York, pp. 331-342. 

Nicotera P. and Lipton S. A. (1999). Excitotoxins in neuronal apoptosis and necrosis. J. Cereb. Blood Flow Metab 19 583-591. 

Lipton, S. A., and Nicotera, P. (1998). Calcium, free radicals and excitotoxins in neuronal apoptosis. 

Disturbances of proton diffusion are not unique to cerebral ischemia. Reduced diffusion has also been found in various experimental conditions including spreading depression (Busch et al. 1995) and peri-infarct depolarizations (Gyngell et al. 1994 Rother et al. 1996), hypoglycemia (Hasegawa et al. 1996), following cortical application of noxious substances [blockers of the Na+-/K+-ATPase (Benveniste et al. 1992), excitotoxins (Verheul et al. 1994)] and... 

Benveniste H. (1991) The excitotoxin hypothesis in relation to cerebral ischemia. Cerebrovasc. Brain Metab. Rev. 3, 213-245. 

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