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

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 β-amyloid_1–42 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 (amyloid_1–42) and those that have no arginine (amyloid_{12–28/22–35}). Enhanced activity of PAD II is noted with free l-arginine.

Keywords::

• Arginine deiminase
• peptidyl arginine deiminase
• neurodegeneration
• Alzheimer's disease
• l-arginine
• β-amyloid plaques

Acknowledgements

Financial support from the Medical Research Council (South Africa) is gratefully acknowledged.