Biological Implications of a Stroke Therapy Based in Neuroglobin Hyaluronate Nanoparticles. Neuroprotective Role and Molecular Bases
Metadatos
Mostrar el registro completo del ítemAutor
Peinado, María Ángeles; Peralta, Sebastián; Morales Hernández, María Encarnación; Ruiz Martínez, AdolfinaEditorial
MDPI
Materia
Neuroglobin Hyaluronate nanoparticles Stroke MCAO Proteomics Neuroprotection
Fecha
2021-12-27Referencia bibliográfica
Peinado, M.Á... [et al.]. 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]
Patrocinador
Spanish Government BFU-2016-80316-RResumen
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.