Arginine deiminases: therapeutic tools in the etiology and pathogenesis of Alzheimer's disease

J Enzyme Inhib Med Chem. 2007 Feb;22(1):121-6. doi: 10.1080/14756360600990829.

Abstract

There is, at present, no definitive pre-mortem diagnostic tool for Alzheimer's disease, (AD) which relates to a poor understanding of its etiology. Brains of AD patients contain large amounts of the toxic plaque-forming beta-amyloid1-42 fragment in addition to elevated concentrations of the amino acid L-arginine. This work proposes that lowering levels of arginine in the astrocytes surrounding amyloid plaques may serve as a therapeutic tool in this neurodegenerative disorder. Arginine deiminase (ADI), from Pseudomonas aeruginosa, and peptidylarginine deiminase [PAD II], from bovine brain, are inhibited by amyloid peptides that contain arginine (amyloid1-42) and those that have no arginine (amyloid12-28/22-35). Enhanced activity of PAD II is noted with free L-arginine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / enzymology
  • Alzheimer Disease / etiology*
  • Alzheimer Disease / pathology
  • Amino Acid Sequence
  • Amyloid beta-Peptides / chemistry
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Hydrolases / therapeutic use*
  • Molecular Sequence Data

Substances

  • Amyloid beta-Peptides
  • Hydrolases
  • arginine deiminase