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Reactive Oxygen Involvement in Neurodegenerative Pathways

Causes, Consequences, and Potential Management with Nitrone-Based Free Radical Traps

  • Chapter
Neuroinflammation

Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

As organs age, the likelihood of severe dysfunction increases steadily. The brain is particularly sensitive to age-related, chronic and acute oxidative pathologies. An emerging paradigm holds that diverse neurodegenerative conditions share a common etiological factor, namely, enhanced brain tissue oxidation owing to exacerbated production of reactive oxygen species (ROS) or to compromise of antioxidant defense and repair mechanisms. Brain is particularly susceptible to oxidative stress owing to its high content of unsaturated lipids, high metabolic rate, relative dearth of antioxidant enzymes, and inability to regenerate lost neurons. Pathogenic ROS generation may result from metabolic enzyme dysregulation, impaired mitochondrial respiration, excitotoxic stimulation, and secondarily as a function of intracellular calcium stress (summarized in Fig. 1 and elaborated below). Natural variation in antioxidant systems may explain why humans differ so greatly with respect to pathways and rates of neurodegeneration. If this is the case, antioxidant supplementation of the aging brain may forestall certain aspects of age-related neurodegeneration. Accordingly, much research has focused on antioxidant management of aging brain and on antioxidant interdiction of postischemic brain damage. Recent findings indicate that specific antioxidants do more than scavenge ROS, but may indirectly affect cellular signal transduction, genetic response, and inflammatory events in such a way as to modulate beneficially brain response to oxidative challenge.

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Authors
  1. Kenneth Hensley
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  2. Quentin N. Pye
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  3. Tahereh Tabatabaie
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  4. Charles A. Stewart
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  5. Robert A. Floyd
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  1. Pharmacology, CoCensys, Inc., Irvine, CA, USA

    Paul L. Wood (Director) (Director)

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Hensley, K., Pye, Q.N., Tabatabaie, T., Stewart, C.A., Floyd, R.A. (1998). Reactive Oxygen Involvement in Neurodegenerative Pathways. In: Wood, P.L. (eds) Neuroinflammation. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-473-3_10

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  • DOI: https://doi.org/10.1007/978-1-59259-473-3_10

  • Publisher Name: Humana Press, Totowa, NJ

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