Role of Metabotropic Glutamate Receptors in Neuronal Degeneration

  • Jitendra Patel
  • William C. Zinkand
Part of the The Receptors book series (REC)


Glutamate is believed to be the key mediator in neurodegenerative processes associated with stroke, epilepsy, and a broad spectrum of neurodegenerative disorders, including, Huntington’ s disease and Alzheimer disease (Choi, 1988; Beal, 1993). The elucidation of the underlying mechanism involved in the pathophysiology of glutamate has been the topic of intensive research. Although the role of glutamate-induced neurotoxicity in chronic neurodegenerative disease remains unclear, compelling evidence suggests that ischemia-triggered neuronal damage is largely attributed to excessive and persistent activation of glutamate receptors (for recent reviews, see Whetsell and Shapira, 1993; Choi, 1988; Beal, 1933). Because glutamate can produce both excitation and toxicity in neurons, the term “excitotoxicity” was proposed by Olney and coworkers (Olney et al., 1978). It is now widely believed that excessive elevation of intracellular calcium is an early and critical step in excitotoxicity (see Fig 1; and Rothman, 1984; Choi, 1988; Garthwaite and Garthwaite, 1986; Frandsen and Schousboe, 1993). In vivo evidence supporting a central role of calcium in excitotoxicity is derived from the observation that calcium accumulates in nervous tissue in cerebral ischemia (Siesjo and Bengtsson, 1989; Simon et al., 1984) and in epilepsy (Meyer, 1989; Uematsu et al., 1990), and that ischemic cell damage can be attenuated by suppression of calcium influx (Pizzi et al., 1991; Valentino et al., 1993) and chelation of intracellular calcium (Tymianski et al., 1993).


Excitatory Amino Acid Metabotropic Glutamate Receptor Cerebellar Granule Cell Metabotropic Receptor Excitatory Amino Acid Receptor 
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© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Jitendra Patel
  • William C. Zinkand

There are no affiliations available

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