Targeting optic nerve citrullination in glaucoma: A role for protein-arginine deiminase 2 (PAD2) inhibitors

Abstract

Protein-arginine deiminase 2 (PAD2, also known as peptidylarginine deiminase 2), a member of the protein-arginine deiminase (PAD) family, converts protein-bound arginine residues to citrulline, a process known as deimination. Using proteomics, PAD2 was detected in glaucomatous eyes as one of the most abundant proteins in the optic nerve compared to controls. Dysregulation of PAD2, leading to elevated levels and consequent aberrant deimination, was observed in response to pressure in vitro and is likely to occur in vivo as well. Experimental in vitro data indicate that, once initiated, dysregulation of PAD2 is not controllable by pressure regulation alone. Aberrant deimination has detrimental consequences at the cellular and tissue levels, implicating PAD2 as an independent target for intervention for neuroprotection in glaucoma. An account of PADs, their involvement in disease and their inhibitors, including PAD2 inhibitors, is presented here. Copyright © 2007 Prous Science.