iRhom1 rescues cognitive dysfunction in multiple sclerosis via preventing myelin injury

Genes Brain Behav. 2021 Nov;20(8):e12771. doi: 10.1111/gbb.12771. Epub 2021 Oct 21.

Abstract

Multiple sclerosis (MS) is characterized by myelin sheath injury. A disintegrin and metalloprotease-17 (ADAM17), a disintegrin and metalloproteinase, is essential in regulating oligodendrocyte (OL) regeneration and remyelination under demyelinating conditions. iRhom1, a highly conserved inactive protease that belongs to the rhomboid family, is one of key regulators for ADAM17 maturation. However, it is unknown whether iRhom1 also plays a role in central neuron system myelination under demyelinating conditions like MS. In this study, we investigated the function of iRhom1/ADAM17 in cognitive capability in MS by establishing the mice with iRhom1 overexpression in the hippocampus.

Keywords: ADAM17; iRhom1; multiple sclerosis; myelination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM17 Protein / metabolism
  • Animals
  • Cognition*
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / metabolism
  • Multiple Sclerosis / physiopathology
  • Myelin Sheath / metabolism
  • Oligodendroglia / metabolism

Substances

  • Membrane Proteins
  • iRhom1 protein, mouse
  • ADAM17 Protein
  • Adam17 protein, mouse