Alternative excitotoxic hypotheses

RL Albin, JT Greenamyre - Neurology, 1992 - AAN Enterprises
Neurology, 1992AAN Enterprises
The concept of excitotoxicity, neuronal death produced by overstimulation of excitatory
ammo acid receptors, has become a popular way of explaining the pathogenesis of
neuronal death in a variety of acute and chronic neurologic diseases. While there is strong
evidence supporting the role of excitotoxicity in acute processes such as hypoxia/ischemia
and hypoglycemia, the role of excitotoxicity in chronic neurologic disease is not firmly
established. To account for the inter-and intraregional variations in pathology of different …
The concept of excitotoxicity, neuronal death produced by overstimulation of excitatory ammo acid receptors, has become a popular way of explaining the pathogenesis of neuronal death in a variety of acute and chronic neurologic diseases. While there is strong evidence supporting the role of excitotoxicity in acute processes such as hypoxia/ischemia and hypoglycemia, the role of excitotoxicity in chronic neurologic disease is not firmly established. To account for the inter- and intraregional variations in pathology of different neurodegenerative disorders, we suggest two modified forms of the excitotoxic hypothesis in which specific populations of neurons become more vulnerable to excitotoxic insult either by (1) possessing abnormal excitatory amino acid receptor subtypes or (2) being afflicted by any disease process that impairs cellular energy metabolism or otherwise decreases neuronal membrane potential. In these ways, excitotoxicity may be a final common pathway of neuronal death in a variety of neurodegenerative diseases.
American Academy of Neurology