Axonal and Myelin Neuroprotection by the Peptoid BN201 in Brain Inflammation

Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics
Pablo VillosladaAngel Messeguer

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.

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Citations

Apr 18, 2020·Expert Opinion on Investigational Drugs·Pablo Villoslada, Lawrence Steinman
Nov 8, 2020·Drugs·Giulia AmoreChiara La Morgia
Aug 21, 2021·Autoimmunity Reviews·Staley A Brod

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Methods Mentioned

BETA
Assay
Biosensor
ELISA
PCR
electron microscopy
Protein Precipitation
thermal shift
flow cytometry

Clinical Trials Mentioned

NCT03630497

Software Mentioned

pION PSR4p
DiscoverX
PathHunter
SPSS
Fiji
GE InCell
ChemInnovation

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