Enhanced Neuron Growth and Electrical Activity by a Supramolecular Netrin-1 Mimetic Nanofiber.

Autor:	Smith CS; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States.; Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, United States., Álvarez Z; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States.; Department of Medicine, Northwestern University, Chicago, Illinois 60611, United States.; Biomaterials for Neural Regeneration, Institute for Bioengineering of Catalonia (IBEC), Barcelona 08028, Spain., Qiu R; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States.; Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States., Sasselli IR; Centro de Fisica de Materiales (CFM), CSIC-UPV/EHU, San Sebastián 20018, Spain., Clemons T; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States.; Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States., Ortega JA; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States.; The Ken & Ruth Davee Department of Neurology, Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, United States.; Department of Pathology and Experimental Therapeutics, Institute of Neurosciences, University of Barcelona, L'Hospitalet de Llobregat, Barcelona 08907, Spain., Vilela-Picos M; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States., Wellman H; Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States., Kiskinis E; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States.; The Ken & Ruth Davee Department of Neurology, Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, United States.; Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, United States., Stupp SI; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States.; Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, United States.; Department of Medicine, Northwestern University, Chicago, Illinois 60611, United States.; Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States.; Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois 60208, United States.
Jazyk:	angličtina
Zdroj:	ACS nano [ACS Nano] 2023 Oct 24; Vol. 17 (20), pp. 19887-19902. Date of Electronic Publication: 2023 Oct 04.
DOI:	10.1021/acsnano.3c04572
Abstrakt:	Neurotrophic factors are essential not only for guiding the organization of the developing nervous system but also for supporting the survival and growth of neurons after traumatic injury. In the central nervous system (CNS), inhibitory factors and the formation of a glial scar after injury hinder the functional recovery of neurons, requiring exogenous therapies to promote regeneration. Netrin-1, a neurotrophic factor, can initiate axon guidance, outgrowth, and branching, as well as synaptogenesis, through activation of deleted in colorectal cancer (DCC) receptors. We report here the development of a nanofiber-shaped supramolecular mimetic of netrin-1 with monomers that incorporate a cyclic peptide sequence as the bioactive component. The mimetic structure was found to activate the DCC receptor in primary cortical neurons using low molar ratios of the bioactive comonomer. The supramolecular nanofibers enhanced neurite outgrowth and upregulated maturation as well as pre- and postsynaptic markers over time, resulting in differences in electrical activity similar to neurons treated with the recombinant netrin-1 protein. The results suggest the possibility of using the supramolecular structure as a therapeutic to promote regenerative bioactivity in CNS injuries.
Databáze:	MEDLINE
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