Inactivation of Protein Tyrosine Phosphatase Receptor Type Z by Pleiotrophin Promotes Remyelination through Activation of Differentiation of Oligodendrocyte Precursor Cells

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Kazuya KuboyamaMasaharu Noda

Abstract

Multiple sclerosis (MS) is a progressive neurological disorder associated with myelin destruction and neurodegeneration. Oligodendrocyte precursor cells (OPCs) present in demyelinated lesions gradually fail to differentiate properly, so remyelination becomes incomplete. Protein tyrosine phosphatase receptor type Z (PTPRZ), one of the most abundant protein tyrosine phosphatases expressed in OPCs, is known to suppress oligodendrocyte differentiation and maintain their precursor cell stage. In the present study, we examined the in vivo mechanisms for remyelination using a cuprizone-induced demyelination model. Ptprz-deficient and wild-type mice both exhibited severe demyelination and axonal damage in the corpus callosum after cuprizone feeding. The similar accumulation of OPCs was observed in the lesioned area in both mice; however, remyelination was significantly accelerated in Ptprz-deficient mice after the removal of cuprizone. After demyelination, the expression of pleiotrophin (PTN), an inhibitory ligand for PTPRZ, was transiently increased in mouse brains, particularly in the neurons involved, suggesting its role in promoting remyelination by inactivating PTPRZ activity. In support of this view, oligodendrocyte differentiati...Continue Reading

Citations

May 24, 2016·Neural Regeneration Research·Francisco José Ruiz-López, Miguel Blanquer
Oct 11, 2017·Journal of Biochemistry·Akihiro FujikawaMasaharu Noda
Aug 6, 2019·Brain Pathology·Alenka MatjašičDanijela Kolenc
Oct 30, 2016·Experimental Neurobiology·Gyun Jee SongKyoungho Suk
Jul 19, 2017·Scientific Reports·Akihiro FujikawaMasaharu Noda
May 7, 2019·Journal of Neuropathology and Experimental Neurology·Caroline Esmonde-WhiteJack P Antel
May 29, 2021·Frontiers in Cell and Developmental Biology·Alexandria N Hughes
Jun 11, 2021·Seminars in Cell & Developmental Biology·Katrina L AdamsWendy B Macklin
Jul 13, 2021·Archives of Medical Research·María Paulina Reyes-MataDaniel Ortuño-Sahagún
Jul 28, 2021·Proceedings of the National Academy of Sciences of the United States of America·Dhananjay YellajoshyulaWilliam T Dauer

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