Axonal and Schwann cell BACE1 is equally required for remyelination of peripheral nerves

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Xiangyou HuRiqiang Yan

Abstract

Inhibition of β-site APP cleaving enzyme 1 (BACE1) is being pursued as a therapeutic target for treating patients with Alzheimer's disease because BACE1 is the sole β-secretase for generating β-amyloid peptide. Knowledge regarding the other cellular functions of BACE1 is therefore critical for the safe use of BACE1 inhibitors in human patients. BACE1 deficiency in mice causes hypomyelination during development and impairs remyelination in injured sciatic nerves. Since BACE1 is expected to be ubiquitously expressed, we asked whether axonal or Schwann cell BACE1 is required for optimal remyelination. By swapping sciatic nerve segments from BACE1-null mice with the corresponding wild-type nerve segments or vice versa, we tested how a deficiency of BACE1 in Schwann cells or axons affects remyelination. Our results show that BACE1 in axons and Schwann cells is similarly important for remyelination of regenerated axons. Nerve injury induces BACE1 transcription and protein levels are elevated in Schwann cells. Expression of type I neuregulin 1 (Nrg1), rather than type III Nrg1, was induced by Schwann cells, and the abolished Nrg1 cleavage in BACE1-null Schwann cells contributed to decreased remyelination of regenerated axons. Hence, t...Continue Reading

Citations

Jan 13, 2016·Proceedings of the National Academy of Sciences of the United States of America·Young Il LeeWesley J Thompson
Oct 8, 2015·Trends in Cell Biology·Giulio Srubek TomassyPaola Arlotta
Oct 16, 2015·Journal of Neurochemistry·Xiangyou HuRiqiang Yan
Apr 30, 2015·Glia·Kelly R MonkCarla Taveggia
Mar 30, 2016·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Genevieve Evin
Jul 9, 2017·Neurobiology of Disease·Carolyn TallonMohamed H Farah
Nov 25, 2017·Neural Regeneration Research·Carolyn Tallon, Mohamed H Farah
Jul 7, 2020·Developmental Neurobiology·Ruth M Stassart, Ashwin Woodhoo
May 5, 2017·Frontiers in Molecular Neuroscience·Riqiang Yan
Apr 3, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Carolyn TallonMohamed H Farah
Apr 6, 2019·Frontiers in Cellular Neuroscience·Marta Pellegatta, Carla Taveggia
Oct 11, 2020·Science Advances·Yutong ZhouBingyang Shi
Mar 17, 2021·Journal of Neuroinflammation·John A Fissel, Mohamed H Farah
Aug 28, 2021·International Journal of Molecular Sciences·Cheng-Shyuan RauChing-Hua Hsieh

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