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Science 29 October 1993:
Vol. 262. no. 5134, pp. 689 - 695
DOI: 10.1126/science.7901908
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Articles

Science, Vol 262, Issue 5134, 689-695
Copyright © 1993 by American Association for the Advancement of Science

articles

Oxidative stress, glutamate, and neurodegenerative disorders

JT Coyle and P Puttfarcken

Department of Psychiatry, Harvard Medical School, Belmont, MA 02178.

There is an increasing amount of experimental evidence that oxidative stress is a causal, or at least an ancillary, factor in the neuropathology of several adult neurodegenerative disorders, as well as in stroke, trauma, and seizures. At the same time, excessive or persistent activation of glutamate-gated ion channels may cause neuronal degeneration in these same conditions. Glutamate and related acidic amino acids are thought to be the major excitatory neurotransmitters in brain and may be utilized by 40 percent of the synapses. Thus, two broad mechanisms--oxidative stress and excessive activation of glutamate receptors--are converging and represent sequential as well as interacting processes that provide a final common pathway for cell vulnerability in the brain. The broad distribution in brain of the processes regulating oxidative stress and mediating glutamatergic neurotransmission may explain the wide range of disorders in which both have been implicated. Yet differential expression of components of the processes in particular neuronal systems may account for selective neurodegeneration in certain disorders.


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Histidines 578 and 587 in the S5-S6 Linker of the Human Ether-a-gogo Related Gene-1 K+ Channels Confer Sensitivity to Reactive Oxygen Species.
A. Pannaccione, P. Castaldo, E. Ficker, L. Annunziato, and M. Taglialatela (2002)
J. Biol. Chem. 277, 8912-8919
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Manganese Superoxide Dismutase Deficiency Exacerbates Cerebral Infarction After Focal Cerebral Ischemia/Reperfusion in Mice: Implications for the Production and Role of Superoxide Radicals.
G. W. Kim, T. Kondo, N. Noshita, and P. H. Chan (2002)
Stroke 33, 809-815
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Protection of HLE B-3 Cells against Hydrogen Peroxide- and Naphthalene-Induced Lipid Peroxidation and Apoptosis by Transfection with hGSTA1 and hGSTA2.
Y. Yang, R. Sharma, J.-Z. Cheng, M. K. Saini, N. H. Ansari, U. P. Andley, S. Awasthi, and Y. C. Awasthi (2002)
Invest. Ophthalmol. Vis. Sci. 43, 434-445
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