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Biological Implications of a Stroke Therapy Based in Neuroglobin Hyaluronate Nanoparticles. Neuroprotective Role and Molecular Bases

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Department of Experimental Biology, Campus de Las Lagunillas s/n, University of Jaén, Building B3, 23071 Jaen, Spain
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BIONAND-Centro Andaluz de Nanomedicina y Biotecnología, Junta de Andalucía, Universidad de Málaga, Parque Tecnológico de Andalucía, 29590 Malaga, Spain
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Department of Pharmacy and Pharmaceutical Technology, Campus de Cartuja s/n, School of Pharmacy, University of Granada, 18071 Granada, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Cristina Angeloni and Andrea Tarozzi
Int. J. Mol. Sci. 2022, 23(1), 247; https://doi.org/10.3390/ijms23010247
Received: 1 December 2021 / Revised: 23 December 2021 / Accepted: 23 December 2021 / Published: 27 December 2021
Exogenous neuroprotective protein neuroglobin (Ngb) cannot cross the blood–brain barrier. To overcome this difficulty, we synthesized hyaluronate nanoparticles (NPs), able to deliver Ngb into the brain in an animal model of stroke (MCAO). These NPs effectively reached neurons, and were microscopically identified after 24 h of reperfusion. Compared to MCAO non-treated animals, those treated with Ngb-NPs showed survival rates up to 50% higher, and better neurological scores. Tissue damage improved with the treatment, but no changes in the infarct volume or in the oxidative/nitrosative values were detected. A proteomics approach (p-value < 0.02; fold change = 0.05) in the infarcted areas showed a total of 219 proteins that significantly changed their expression after stroke and treatment with Ngb-NPs. Of special interest, are proteins such as FBXO7 and NTRK2, which were downexpressed in stroke, but overexpressed after treatment with Ngb-NPs; and ATX2L, which was overexpressed only under the effect of Ngb. Interestingly, the proteins affected by the treatment with Ngb were involved in mitochondrial function and cell death, endocytosis, protein metabolism, cytoskeletal remodeling, or synaptic function, and in regenerative processes, such as dendritogenesis, neuritogenesis, or sinaptogenesis. Consequently, our pharmaceutical preparation may open new therapeutic scopes for stroke and possibly for other neurodegenerative pathologies. View Full-Text
Keywords: neuroglobin; hyaluronate nanoparticles; stroke; MCAO; proteomics; neuroprotection neuroglobin; hyaluronate nanoparticles; stroke; MCAO; proteomics; neuroprotection
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MDPI and ACS Style

Peinado, M.Á.; Ovelleiro, D.; del Moral, M.L.; Hernández, R.; Martínez-Lara, E.; Siles, E.; Pedrajas, J.R.; García-Martín, M.L.; Caro, C.; Peralta, S.; Morales, M.E.; Ruiz, M.A.; Blanco, S. Biological Implications of a Stroke Therapy Based in Neuroglobin Hyaluronate Nanoparticles. Neuroprotective Role and Molecular Bases. Int. J. Mol. Sci. 2022, 23, 247. https://doi.org/10.3390/ijms23010247

AMA Style

Peinado MÁ, Ovelleiro D, del Moral ML, Hernández R, Martínez-Lara E, Siles E, Pedrajas JR, García-Martín ML, Caro C, Peralta S, Morales ME, Ruiz MA, Blanco S. Biological Implications of a Stroke Therapy Based in Neuroglobin Hyaluronate Nanoparticles. Neuroprotective Role and Molecular Bases. International Journal of Molecular Sciences. 2022; 23(1):247. https://doi.org/10.3390/ijms23010247

Chicago/Turabian Style

Peinado, María Á., David Ovelleiro, María L. del Moral, Raquel Hernández, Esther Martínez-Lara, Eva Siles, José R. Pedrajas, María L. García-Martín, Carlos Caro, Sebastián Peralta, María E. Morales, María A. Ruiz, and Santos Blanco. 2022. "Biological Implications of a Stroke Therapy Based in Neuroglobin Hyaluronate Nanoparticles. Neuroprotective Role and Molecular Bases" International Journal of Molecular Sciences 23, no. 1: 247. https://doi.org/10.3390/ijms23010247

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