Consequences of Calcium Overload

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Entry of calcium through the NMDA (and similar channels) can be devastating. First, attempts to get rid of the excess calcium use up already scarce supplies of ATP. Second, excessive calcium influx causes the disordered activation of a wide range of enzyme systems (proteases, lipases, and nucleases). These enzymes and their metabolic products, such as oxygen free radicals, damage cell membranes, genetic material, and structural proteins in the neurons, ultimately leading to cell death. This sequence of events has been termed excitotoxicity because of the pivotal role of excitatory amino acids such as glutamate.

Several agents are under investigation to block these steps.

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