Novel inhibitors of iron‐dependent lipid peroxidation for neurodegenerative disorders

Edward D. Hall

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

A considerable body of information supports the occurrence and pathophysiological importance of oxygen radicalmediated lipid peroxidation in acute cerebral damage secondary to traumatic or ischemic injury. Moreover, peroxidative mechanisms have been implicated in chronic neurodegenerative (e.g., Alzheimer's and Parkinson's diseases) and demyelinating (e.g., multiple sclerosis) disorders. Consequently, there has been interest in identification of pharmacological agents with potent ability to interrupt oxygen radical formation or cell membrane lipid peroxidative mechanisms. Our laboratories have developed a novel series of potent lipid peroxidation inhibitors known as the 21‐aminosteroids or “lazaroids.” One of these compounds, U‐74006F or tirilazad mesylate, has shown efficacy in animal models of brain injury and focal cerebral ischemia. In addition, the compound has been found to attenuate the increased lipid peroxidation observed in Alzheimer's brain tissue, to retard anterograde degeneration of motor nerve fibers, and to be effective in decreasing the clinical disease severity and blood‐brain barrier disruption observed in the multiple sclerosis model of experimental allergic encephalomyelitis. Another series of antioxidants, the 2‐methylaminochromans typified by the compound U‐78517F, have been discovered that are even more potent and effective inhibitors of lipid peroxidation than the 21‐aminosteroids.

Original languageEnglish
Pages (from-to)S137-S142
JournalAnnals of Neurology
Volume32
Issue number1 S
DOIs
StatePublished - 1992

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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