Targeting Fibronectin to Overcome Remyelination Failure in Multiple Sclerosis: The Need for Brain- and Lesion-Targeted Drug Delivery

Pauline E M van Schaik, Inge S Zuhorn*, Wia Baron

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

11 Citations (Scopus)
77 Downloads (Pure)

Abstract

Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease with unknown etiology that can be characterized by the presence of demyelinated lesions. Prevailing treatment protocols in MS rely on the modulation of the inflammatory process but do not impact disease progression. Remyelination is an essential factor for both axonal survival and functional neurological recovery but is often insufficient. The extracellular matrix protein fibronectin contributes to the inhibitory environment created in MS lesions and likely plays a causative role in remyelination failure. The presence of the blood-brain barrier (BBB) hinders the delivery of remyelination therapeutics to lesions. Therefore, therapeutic interventions to normalize the pathogenic MS lesion environment need to be able to cross the BBB. In this review, we outline the multifaceted roles of fibronectin in MS pathogenesis and discuss promising therapeutic targets and agents to overcome fibronectin-mediated inhibition of remyelination. In addition, to pave the way for clinical use, we reflect on opportunities to deliver MS therapeutics to lesions through the utilization of nanomedicine and discuss strategies to deliver fibronectin-directed therapeutics across the BBB. The use of well-designed nanocarriers with appropriate surface functionalization to cross the BBB and target the lesion sites is recommended.

Original languageEnglish
Article number8418
Number of pages38
JournalInternational Journal of Molecular Sciences
Volume23
Issue number15
DOIs
Publication statusPublished - Aug-2022

Keywords

  • blood-brain barrier
  • extracellular matrix
  • fibronectin
  • liposomes
  • multiple sclerosis
  • nanomedicine
  • oligodendrocytes
  • PLGA
  • remyelination
  • therapeutic targets
  • CENTRAL-NERVOUS-SYSTEM
  • CHONDROITIN SULFATE PROTEOGLYCANS
  • BASEMENT-MEMBRANE PROTEINS
  • EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS
  • MAGNETIC-RESONANCE ELASTOGRAPHY
  • CUPRIZONE-INDUCED DEMYELINATION
  • ENDOTHELIAL-CELL PROLIFERATION
  • VASCULAR SMOOTH-MUSCLE
  • EXTRACELLULAR-MATRIX
  • IN-VITRO

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