2 min read

ID: 1171579

Short Link: https://gregory-ms.com/articles/1171579/

Discovery Date: 08 January 2023, 01:30:18 UTC

Published Date: 2023-01-07 00:00:00

Source: BioMedCentral

Link: https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-022-02686-6

Manual Selection: true

Machine Learning Gaussian Naive Bayes Model: false

Abstract

jats:titleAbstract</jats:title>jats:sec jats:titleBackground</jats:title> jats:pPromotion of myelin repair in the context of demyelinating diseases such as multiple sclerosis (MS) still represents a clinical unmet need, given that this disease is not only characterized by autoimmune activities but also by impaired regeneration processes. Hence, this relates to replacement of lost oligodendrocytes and myelin sheaths—the primary targets of autoimmune attacks. Endogenous remyelination is mainly mediated via activation and differentiation of resident oligodendroglial precursor cells (OPCs), whereas its efficiency remains limited and declines with disease progression and aging. Teriflunomide has been approved as a first-line treatment for relapsing remitting MS. Beyond its role in acting via inhibition of de novo pyrimidine synthesis leading to a cytostatic effect on proliferating lymphocyte subsets, this study aims to uncover its potential to foster myelin repair.</jats:p> </jats:sec>jats:sec jats:titleMethods</jats:title> jats:pWithin the cuprizone mediated de-/remyelination model teriflunomide dependent effects on oligodendroglial homeostasis and maturation, related to cellular processes important for myelin repair were analyzed in vivo. Teriflunomide administration was performed either as pulse or continuously and markers specific for oligodendroglial maturation and mitochondrial integrity were examined by means of gene expression and immunohistochemical analyses. In addition, axon myelination was determined using electron microscopy.</jats:p> </jats:sec>jats:sec jats:titleResults</jats:title> jats:pBoth pulse and constant teriflunomide treatment efficiently boosted myelin repair activities in this model, leading to accelerated generation of oligodendrocytes and restoration of myelin sheaths. Moreover, teriflunomide restored mitochondrial integrity within oligodendroglial cells.</jats:p> </jats:sec>jats:sec jats:titleConclusions</jats:title> jats:pThe link between de novo pyrimidine synthesis inhibition, oligodendroglial rescue, and maintenance of mitochondrial homeostasis appears as a key for successful myelin repair and hence for protection of axons from degeneration.</jats:p> </jats:sec>

Noun Phrases in Title

  • a therapeutic means
  • myelin repair
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