Preprint Review Version 1 This version is not peer-reviewed

Peptidylarginine Deiminases as Mediators of Microvesicular Release - Novel Therapeutic Interventions

Version 1 : Received: 16 March 2017 / Approved: 16 March 2017 / Online: 16 March 2017 (17:54:15 CET)

How to cite: Lange, S.; Kholia, S.; Kosgodage, U.; Hristova, M.; Hardy, J.; Inal, J.M. Peptidylarginine Deiminases as Mediators of Microvesicular Release - Novel Therapeutic Interventions. Preprints 2017, 2017030125 (doi: 10.20944/preprints201703.0125.v1). Lange, S.; Kholia, S.; Kosgodage, U.; Hristova, M.; Hardy, J.; Inal, J.M. Peptidylarginine Deiminases as Mediators of Microvesicular Release - Novel Therapeutic Interventions. Preprints 2017, 2017030125 (doi: 10.20944/preprints201703.0125.v1).

Abstract

Extracellular vesicle (EV) release, which occurs in most eukaryotic cells, has recently been associated with peptidylarginine deiminase (PAD)-driven protein deimination. Evidence points to the involvement of deiminated cytoskeletal proteins and changes in histone deimination. Both PADs and EVs are associated with various pathologies including cancers, autoimmune and neurodegenerative diseases. The elevated PAD expression observed in cancers may contribute to increase in EV shedding observed from cancer cells, contributing to cancer progression. Similarly, elevated PAD expression observed in neurodegenerative diseases may cause increased EV shedding and spread of neurodegenerative EV cargo, contributing to disease progression and pathologies. Pharmacological inhibition of PAD-mediated deimination using pan-PAD inhibitor Cl-amidine, reduced cellular EV release in prostate cancer cells, rendering them significantly more susceptible to chemotherapeutic drugs. Studies on models of central nervous system damage have demonstrated critical functional roles for PADs and neuroprotective effects using PAD inhibitors in vivo, while human neurodegenerative iPSC in vitro models showed evidence of increased protein deimination. Besides using refined PAD inhibitors to selectively manipulate EV biogenesis for novel combination therapies in cancer treatment, we also speculate how EV biogenesis could be targeted via the newly identified PAD-pathway to ameliorate neurodegenerative disease progression.

Subject Areas

Extracellular vesicles (EVs); Peptidylarginine deiminases (PADs); Chlor-amidine (Cl-Am); cancer; neurodegeneration; deimination; cytoskeleton; induced pluripotent stem cells (iPSCs); histone H3; epigenetics

Readers' Comments and Ratings (0)

Leave a public comment
Send a private comment to the author(s)
Rate this article
Views 0
Downloads 0
Comments 0
Metrics 0
Leave a public comment

×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.