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Review
. 2013 Jan-Feb;7(1):42-6.
doi: 10.4161/pri.22380. Epub 2012 Sep 28.

Peptidylarginine deiminase and protein citrullination in prion diseases: strong evidence of neurodegeneration

Byungki Jang  1 , Akihito Ishigami, Naoki Maruyama, Richard I Carp, Yong-Sun Kim, Eun-Kyoung Choi
Affiliations
Review

Peptidylarginine deiminase and protein citrullination in prion diseases: strong evidence of neurodegeneration

Byungki Jang et al. Prion. 2013 Jan-Feb.

Abstract

The post-translational citrullination (deimination) process is mediated by peptidylarginine deiminases (PADs), which convert peptidylarginine into peptidylcitrulline in the presence of high calcium concentrations. Over the past decade, PADs and protein citrullination have been commonly implicated as abnormal pathological features in neurodegeneration and inflammatory responses associated with diseases such as multiple sclerosis, Alzheimer disease and rheumatoid arthritis. Based on this evidence, we investigated the roles of PADs and citrullination in the pathogenesis of prion diseases. Prion diseases (also known as transmissible spongiform encephalopathies) are fatal neurodegenerative diseases that are pathologically well characterized as the accumulation of disease-associated misfolded prion proteins, spongiform changes, glial cell activation and neuronal loss. We previously demonstrated that the upregulation of PAD2, mainly found in reactive astrocytes of infected brains, leads to excessive citrullination, which is correlated with disease progression. Further, we demonstrated that various cytoskeletal and energy metabolism-associated proteins are particularly vulnerable to citrullination. Our recent in vivo and in vitro studies elicited altered functions of enolase as the result of citrullination; these altered functions included reduced enzyme activity, increased protease sensitivity and enhanced plasminogen-binding affinity. These findings suggest that PAD2 and citrullinated proteins may play a key role in the brain pathology of prion diseases. By extension, we believe that abnormal increases in protein citrullination may be strong evidence of neurodegeneration.

Keywords: citrullination; enolase; neurodegeneration; peptidylarginine deiminase; prion.

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Figures

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Figure 1. An outline of the protein citrullination (deimination) process. Calcium-dependent peptidylarginine deiminases (PADs) convert peptidylarginine into peptidylcitrulline, resulting in altered protein function.
See this image and copyright information in PMC

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References

    1. Prusiner SB. Prions. Proc Natl Acad Sci U S A. 1998;95:13363–83. doi: 10.1073/pnas.95.23.13363. - DOI - PMC - PubMed
    1. Aguzzi A, Sigurdson C, Heikenwaelder M. Molecular mechanisms of prion pathogenesis. Annu Rev Pathol. 2008;3:11–40. doi: 10.1146/annurev.pathmechdis.3.121806.154326. - DOI - PubMed
    1. Puoti G, Bizzi A, Forloni G, Safar JG, Tagliavini F, Gambetti P. Sporadic human prion diseases: molecular insights and diagnosis. Lancet Neurol. 2012;11:618–28. doi: 10.1016/S1474-4422(12)70063-7. - DOI - PubMed
    1. Jang B, Kim E, Choi JK, Jin JK, Kim JI, Ishigami A, et al. Accumulation of citrullinated proteins by up-regulated peptidylarginine deiminase 2 in brains of scrapie-infected mice: a possible role in pathogenesis. Am J Pathol. 2008;173:1129–42. doi: 10.2353/ajpath.2008.080388. - DOI - PMC - PubMed
    1. Jang B, Jin JK, Jeon YC, Cho HJ, Ishigami A, Choi KC, et al. Involvement of peptidylarginine deiminase-mediated post-translational citrullination in pathogenesis of sporadic Creutzfeldt-Jakob disease. Acta Neuropathol. 2010;119:199–210. doi: 10.1007/s00401-009-0625-x. - DOI - PubMed

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