Axonal and Myelin Neuroprotection by the Peptoid BN201 in Brain Inflammation

Neurotherapeutics. 2019 Jul;16(3):808-827. doi: 10.1007/s13311-019-00717-4.


The development of neuroprotective therapies is a sought-after goal. By screening combinatorial chemical libraries using in vitro assays, we identified the small molecule BN201 that promotes the survival of cultured neural cells when subjected to oxidative stress or when deprived of trophic factors. Moreover, BN201 promotes neuronal differentiation, the differentiation of precursor cells to mature oligodendrocytes in vitro, and the myelination of new axons. BN201 modulates several kinases participating in the insulin growth factor 1 pathway including serum-glucocorticoid kinase and midkine, inducing the phosphorylation of NDRG1 and the translocation of the transcription factor Foxo3 to the cytoplasm. In vivo, BN201 prevents axonal and neuronal loss, and it promotes remyelination in models of multiple sclerosis, chemically induced demyelination, and glaucoma. In summary, we provide a new promising strategy to promote neuroaxonal survival and remyelination, potentially preventing disability in brain diseases.

Keywords: Neuroprotection; glaucoma; multiple sclerosis; neurodegenerative diseases; neuroinflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / therapeutic use*
  • Animals
  • Axons / drug effects*
  • Disease Models, Animal
  • Encephalitis / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy
  • Female
  • Fluorescent Antibody Technique
  • Glaucoma / drug therapy
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myelin Sheath / drug effects*
  • Neuroprotective Agents / therapeutic use*
  • Optic Nerve / drug effects
  • Peptoids / therapeutic use*
  • Proguanil
  • Pyrrolidinones / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Triazines


  • Amides
  • Neuroprotective Agents
  • Peptoids
  • Pyrrolidinones
  • Triazines
  • cycloguanil
  • Proguanil