Arginine deiminases: therapeutic tools in the etiology and pathogenesis of Alzheimer's disease.
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.
Louw
Cassandra
C
Department of Biochemistry, Microbiology and Biotechnology Rhodes University, Grahamstown, South Africa.
Gordon
Alon
A
Johnston
Nicolette
N
Mollatt
Carolyn
C
Bradley
Graeme
G
Whiteley
Chris G
CG
D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D006867:Hydrolases / Q000627:therapeutic use*; D008969:Molecular Sequence Data
D016229:Amyloid beta-Peptides; D006867:Hydrolases; C019723:arginine deiminase