Peptidylarginine Deiminases-Roles in Cancer and Neurodegeneration and Possible Avenues for Therapeutic Intervention via Modulation of Exosome and Microvesicle (EMV) Release?

Int J Mol Sci. 2017 Jun 5;18(6):1196. doi: 10.3390/ijms18061196.

Abstract

Exosomes and microvesicles (EMVs) are lipid bilayer-enclosed structures released from cells and participate in cell-to-cell communication via transport of biological molecules. EMVs play important roles in various pathologies, including cancer and neurodegeneration. The regulation of EMV biogenesis is thus of great importance and novel ways for manipulating their release from cells have recently been highlighted. One of the pathways involved in EMV shedding is driven by peptidylarginine deiminase (PAD) mediated post-translational protein deimination, which is calcium-dependent and affects cytoskeletal rearrangement amongst other things. Increased PAD expression is observed in various cancers and neurodegeneration and may contribute to increased EMV shedding and disease progression. Here, we review the roles of PADs and EMVs in cancer and neurodegeneration.

Keywords: Chlor-amidine (Cl-Am); cancer; cytoskeleton; deimination; epigenetics; exosomes; extracellular vesicles (EVs); histone H3; induced pluripotent stem cells (iPSCs); microvesicles (MVs); neurodegeneration; peptidylarginine deiminases (PADs).

Publication types

  • Review

MeSH terms

  • Animals
  • Cell-Derived Microparticles / metabolism*
  • Central Nervous System / drug effects
  • Central Nervous System / metabolism
  • Central Nervous System / pathology
  • Cytoskeleton / metabolism
  • Enzyme Inhibitors / pharmacology
  • Epigenesis, Genetic
  • Exosomes / metabolism*
  • Extracellular Vesicles / metabolism
  • Histones / metabolism
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / therapy
  • Neuroprotective Agents / pharmacology
  • Protein Binding
  • Protein Processing, Post-Translational
  • Protein-Arginine Deiminases / antagonists & inhibitors
  • Protein-Arginine Deiminases / metabolism*

Substances

  • Enzyme Inhibitors
  • Histones
  • Neuroprotective Agents
  • Protein-Arginine Deiminases