Progranulin: A conductor of receptors orchestra, a chaperone of lysosomal enzymes and a therapeutic target for multiple diseases

Cytokine Growth Factor Rev. 2019 Feb:45:53-64. doi: 10.1016/j.cytogfr.2019.01.002. Epub 2019 Jan 30.

Abstract

Progranulin (PGRN), a widely expressed glycoprotein with pleiotropic function, has been linked to a host of physiological processes and diverse pathological states. A series of contemporary preclinical disease models and clinical trials have evaluated various therapeutic strategies targeting PGRN, highlighting PGRN as a promising therapeutic target. Herein we summarize available knowledge of PGRN targeting in various kinds of diseases, including common neurological diseases, inflammatory autoimmune diseases, cancer, tissue repair, and rare lysosomal storage diseases, with a focus on the functional domain-oriented drug development strategies. In particular, we emphasize the role of extracellular PGRN as a non-conventional, extracellular matrix bound, growth factor-like conductor orchestrating multiple membrane receptors and intracellular PGRN as a chaperone/co-chaperone that mediates the folding and traffic of its various binding partners.

Keywords: Autoimmune diseases; Cancer; Inflammation; Lysosomal storage diseases; Membrane receptors; Neurodegenerative diseases; Progranulin.

Publication types

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

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy*
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Drug Development
  • Humans
  • Inflammation / drug therapy
  • Lysosomal Storage Diseases / drug therapy*
  • Lysosomes / enzymology
  • Mice
  • Molecular Chaperones / physiology
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Nervous System Diseases / drug therapy*
  • Neurodegenerative Diseases / drug therapy
  • Progranulins / physiology*

Substances

  • Molecular Chaperones
  • Progranulins