Renalase: its role as a cytokine, and an update on its association with type 1 diabetes and ischemic stroke

Curr Opin Nephrol Hypertens. 2014 Sep;23(5):513-8. doi: 10.1097/MNH.0000000000000044.

Abstract

Purpose of review: Remarkable progress has been achieved over the past 2 years in understanding the cellular actions of renalase, its pathophysiology and potential therapeutic utility.

Recent findings: There has been a paradigm shift in our thinking about the mechanisms underlying the cellular actions of renalase. We now understand that, independent of its enzymatic properties, renalase functions as a signaling molecule, a cytokine that interacts with a yet-to-be identified plasma membrane receptor(s) to activate protein kinase B and the mitogen-activated protein kinase pathway. These signaling properties are critical to its cytoprotective effects. New information regarding renalase's enzymatic function as an α-nicotinamide adenine dinucleotide oxidase/anomerase will be reviewed. Lastly, we will discuss the association of certain single nucleotide polymorphisms in the renalase gene with type 1 diabetes and with ischemic stroke, and the clinical implications of these findings.

Summary: The consistent association of renalase single nucleotide polymorphisms and the development of type 1 diabetes is a great interest particularly because we now understand that renalase functions as a cytokine. Future work on renalase should focus on exploring the identity of its receptor(s), and its potential role as an immune modulator.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Brain Ischemia / enzymology*
  • Brain Ischemia / genetics
  • Cytokines / metabolism*
  • Diabetes Mellitus, Type 1 / enzymology*
  • Diabetes Mellitus, Type 1 / genetics
  • Dopamine / metabolism
  • Genetic Predisposition to Disease
  • Humans
  • Monoamine Oxidase / metabolism*
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Signal Transduction
  • Stroke / enzymology*

Substances

  • Cytokines
  • Monoamine Oxidase
  • renalase
  • Dopamine