Proteomics Implicates Peptidyl Arginine Deiminase 2 and Optic Nerve Citrullination in Glaucoma Pathogenesis

Abstract

Current results support translational modulation of PAD2 expression and a possible role for the enzyme in POAG optic nerve damage through citrullination and structural disruption of myelination.

Peptidylarginine deiminase and protein citrullination in prion diseases

“…Increased PAD expression and protein citrullination are commonly observed in several neurodegenerative diseases, including MS, AD, optic glaucoma and Parkinson disease, and in psoriasis, rheumatoid arthritis (RA) and cancer. [4][5][6][7]20,[31][32][33][34] In AD patients, the abnormal accumulation of citrullinated proteins and increased PAD2 expression are seen in the hippocampus, where vimentin and GFAP have been identified as PAD substrates. 6 Citrullinated proteins have also been observed in the cytoplasm of the substantia nigra dopamine neurons in Parkinson disease patients.…”

Age‐related reduction in retinal deimination levels in the F344BN rat

“…Protein deimination is known to occur in epidermal, muscle and neuronal tissues. PAD1, 3 catalyze deimination in the skin; PAD2, the major PAD in the eye and brain; and PAD4 is nuclear and ubiquitous (Asaga & Ishigami, 2001;Vossenaar et al ., 2003;Bhattacharya et al ., 2006b). PAD4 activation was suggested to result in transcriptional repression (Wang et al ., 2004).…”

“…Elevated levels of PAD2 and protein deimination have been found in rheumatoid arthritis (Scofield, 2004), and in several human neurological diseases such as multiple sclerosis (Moscarello et al ., 2002), autoimmune encephalomyelitis (Nicholas et al ., 2005), Alzheimer's (Maruyama et al ., 2005;Louw et al ., 2007), amyotrophic lateral sclerosis (Chou et al ., 1996) and glaucoma (Bhattacharya et al ., 2006a, b). Using proteomic mass spectrometry, PAD2 was recently identified in the optic nerve of glaucomatous donors but not in normal controls (Bhattacharya et al ., 2006b). Only a handful of proteins: keratin, myelin basic protein (MBP), glial fibrillary acidic protein, vimentin, trichohyalin, histones (H2A, H3 and H4), filaggrin and fibrinogen are currently known to undergo deimination (Algeciras & Bhattacharya, 2007).…”

Peptidylarginine Deiminases and Protein Deimination in Skin Physiopathology

“…Myelin basic protein, glial fibrillary acidic protein and vimentin are its known substrates. PAD2 is thought to play a role in the onset and progression of neurodegenerative human disorders, including Alzheimer disease and multiple sclerosis, and it has also been implicated in glaucoma pathogenesis (Bhattacharya et al, 2006;Moscarello et al, 2007;Cafaro et al, 2010). Human PAD3 modulates hair follicle structural proteins, such as trichohyalin and S100A3 in the inner root sheath (Rogers et al, 1997;Kanno et al, 2000;Kizawa et al, 2008).…”