Factors that retard remyelination in multiple sclerosis with a focus on TIP30: A novel therapeutic target

Jin Nakahara, Sadakazu Aiso, Norihiro Suzuki

Research output: Contribution to journalReview article

10 Citations (Scopus)

Abstract

In the CNS oligodendrocytes produce myelin and ensheath individual axons after birth. Demyelination disables saltatory conduction and leads to loss of neural functions. Oligodendrocyte precursor cells (OPCs) are immature and abundant reservoir cells in the adult brain that are capable of differentiating into myelinating oligodendrocytes. Upon demyelination insults, OPCs are spontaneously induced to differentiate in order to remyelinate denuded axons and promote functional recovery. While remyelination is an efficient regenerative process in the CNS, it often fails in the chronic phase of multiple sclerosis (MS). OPCs are nonetheless preserved in many MS lesions, suggesting that arrested OPC differentiation underlies remyelination failure in chronic MS. Understanding the molecular pathology of this arrested differentiation and remyelination failure in chronic MS is critical for developing remyelination medicines that will promote a full functional recovery in these patients. Recently, TIP30 was identified as an inhibitor of OPC differentiation in MS. TIP30 inhibits proper nucleocytoplasmic transport and thus disables nuclear import of transcription factors that are required for differentiation. TIP30 may also increase susceptibility of OPCs to cell death. In this review, we examine the pathophysiological nature of remyelination failure in chronic MS and discuss the role of TIP30 as a novel therapeutic target.

Original languageEnglish
Pages (from-to)1375-1386
Number of pages12
JournalExpert Opinion on Therapeutic Targets
Volume13
Issue number12
DOIs
Publication statusPublished - 2009 Dec 1
Externally publishedYes

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Keywords

  • differentiation arrest
  • importin β
  • multiple sclerosis
  • nucleocytoplasmic transport
  • oligodendrocyte precursor cells
  • remyelination failure
  • TIP30

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

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