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

Axonal and Myelin Neuroprotection by the Peptoid BN201 in Brain Inflammation.

Author information

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.

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

PMID:
30815844
PMCID:
PMC6694325
[Available on 2020-07-01]
DOI:
10.1007/s13311-019-00717-4

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