Excitotoxicity enzymic activities involved

Table 5.1 Stimulatory effect of glutamate-mediated Ca2+ influx on enzymic activities involved in excitotoxicity...

The last phase of the excitotoxic cascade involves the activation of various biochemical pathways, among which phospholipases, proteases (in particular cal-pain), kinases and calmodulin-regulated enzymes such as nitric oxide synthase (NOS) play a prominent role. 

Ca2+ influx mediates excitotoxicity with a cascade of events involving free radical generation, mitochondrial dysfunction, and the activation of many enzymes (Table 7.1), including those involved in the generation and metabolism of arachi-donic acid (Farooqui and Horrocks, 1991,1994b Farooqui et al., 2001 Wang et al.,... 

The mechanism of cell loss involves excitotoxicity provoked by intense neuronal firing (Grisar, 1986). There is excessive excitatory neurotransmitter release by activation of N-methyl-D-aspartate (NMDA) receptors and voltage-activated calcium channels which enables intracellular calcium influx in the neurons and glia. This calcium influx leads to a cascade of biochemical processes that ultimately lead to cell death mitochondrial dysfunction with uncoupling of oxidative phosphorylation, generation of reactive oxygen species, and activation of many proteolytic and catabolic enzymes that adversely affect cell function. 

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