The protective role of prosaposin and its receptors in the nervous system

Brain Res. 2014 Oct 17:1585:1-12. doi: 10.1016/j.brainres.2014.08.022. Epub 2014 Aug 15.

Abstract

Prosaposin (also known as SGP-1) is an intriguing multifunctional protein that plays roles both intracellularly, as a regulator of lysosomal enzyme function, and extracellularly, as a secreted factor with neuroprotective and glioprotective effects. Following secretion, prosaposin can undergo endocytosis via an interaction with the low-density lipoprotein-related receptor 1 (LRP1). The ability of secreted prosaposin to promote protective effects in the nervous system is known to involve activation of G proteins, and the orphan G protein-coupled receptors GPR37 and GPR37L1 have recently been shown to mediate signaling induced by both prosaposin and a fragment of prosaposin known as prosaptide. In this review, we describe recent advances in our understanding of prosaposin, its receptors and their importance in the nervous system.

Keywords: GPCR; Lysosome; Myelination; Nerve; Neuroprotection; Neurotrophic.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain Ischemia / metabolism
  • Dopaminergic Neurons / metabolism
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-1 / metabolism*
  • Lysosomes / metabolism
  • Nerve Growth Factors / metabolism*
  • Nerve Regeneration
  • Nervous System / metabolism
  • Neuroglia / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • Saposins / metabolism*
  • Signal Transduction

Substances

  • GPR37 receptor, human
  • LRP1 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Nerve Growth Factors
  • PSAP protein, human
  • Receptors, G-Protein-Coupled
  • Saposins
  • prosaptide