Peptidylarginine Deiminase and Alzheimer's Disease

J Alzheimers Dis. 2022;85(2):473-484. doi: 10.3233/JAD-215302.

Abstract

Peptidylarginine deiminases (PADs) are indispensable enzymes for post-translational modification of proteins, which can convert Arg residues on the surface of proteins to citrulline residues. The PAD family has five isozymes, PAD1, 2, 3, 4, and 6, which have been found in multiple tissues and organs. PAD2 and PAD4 were detected in cerebral cortex and hippocampus from human and rodent brain. In the central nervous system, abnormal expression and activation of PADs are involved in the pathological changes and pathogenesis of Alzheimer's disease (AD). This article reviews the classification, distribution, and function of PADs, with an emphasis on the relationship between the abnormal activation of PADs and AD pathogenesis, diagnosis, and the therapeutic potential of PADs as drug targets for AD.

Keywords: Alzheimer’s disease; PAD inhibitors; citrulline; peptidylarginine deiminases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Animals
  • Cerebral Cortex / metabolism
  • Citrulline / metabolism
  • Hippocampus / metabolism
  • Humans
  • Isoenzymes / metabolism
  • Protein Processing, Post-Translational
  • Protein-Arginine Deiminases / metabolism*

Substances

  • Isoenzymes
  • Citrulline
  • Protein-Arginine Deiminases