2. Academic Validation
  3. Axonal and Myelin Neuroprotection by the Peptoid BN201 in Brain Inflammation

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.
Pablo Villoslada 1,  Gemma Vila 2,  Valeria Colafrancesco 2,  Beatriz Moreno 2,  Begoña Fernandez-Diez 2,  Raquel Vazquez 2,  Inna Pertsovskaya 2,  Irati Zubizarreta 2,  Irene Pulido-Valdeolivas 2,  Joaquin Messeguer 3,  Gloria Vendrell-Navarro 3,  Jose Maria Frade 4,  Noelia López-Sánchez 4,  Meritxell Teixido 5,  Ernest Giralt 5,  Mar Masso 6,  Jason C Dugas 7,  Dmitri Leonoudakis 7,  Karen D Lariosa-Willingham 7,  Lawrence Steinman 8,  Angel Messeguer 3
Affiliations

Affiliations

  • 1 Center for Neuroimmunology, Institut d'Investigacions Biomediques August Pi Sunyer, Casanova 145, Centre Cellex 3A, 08036, Barcelona, Spain. pvilloslada@clinic.ub.es.
  • 2 Center for Neuroimmunology, Institut d'Investigacions Biomediques August Pi Sunyer, Casanova 145, Centre Cellex 3A, 08036, Barcelona, Spain.
  • 3 Institute for Advanced Chemistry of Catalonia, Consejo Superior de Investigaciones Cientificas, Barcelona, 08034, Spain.
  • 4 Instituto Cajal, Consejo Superior de Investigaciones Cientificas, Madrid, 28002, Spain.
  • 5 Institute for Research in Biomedicine, Barcelona, 08028, Spain.
  • 6 Bionure Farma SL, Barcelona, 94025, Spain.
  • 7 Myelin Repair Foundation, Saratoga, NY, 94085, USA.
  • 8 Stanford University, Palo Alto, CA, 94305, USA.
PMID: 30815844 DOI: 10.1007/s13311-019-00717-4
Abstract

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.

Figures
Products