Protein aggregation, metals and oxidative stress in neurodegenerative diseases

B. J. Tabner, O. M.A. El-Agnaf, M. J. German, N. J. Fullwood, D. Allsop

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Abstract

There is clear evidence implicating oxidative stress in the pathology of many different neurodegenerative diseases. ROS (reactive oxygen species) are the primary mediators of oxidative stress and many of the aggregating proteins and peptides associated with neurodegenerative disease can generate hydrogen peroxide, a key ROS, apparently through interactions with redox-active metal ions. Our recent results suggest that ROS are generated during the very early stages of protein aggregation, when protofibrils or soluble oligomers are present, but in the absence of mature amyloid fibrils. The generation of ROS during early-stage protein aggregation may be a common, fundamental molecular mechanism underlying the pathogenesis of oxidative damage, neurodegeneration and cell death in several different neurodegenerative diseases. Drugs that specifically target this process could be useful in the future therapy of these diseases.

Original languageEnglish
Pages (from-to)1082-1086
Number of pages5
JournalBiochemical Society Transactions
Volume33
Issue number5
DOIs
Publication statusPublished - 1 Nov 2005

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Keywords

  • Amyloid
  • Hydrogen peroxide
  • Metal
  • Neurodegeneration
  • Oligomer
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry

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