Intranasal PRGF-Endoret enhances neuronal survival and attenuates NF-κB-dependent inflammation process in a mouse model of Parkinson's disease

• Published in: Journal of controlled release Vol. 203; pp. 170 - 180
• Main Authors: Anitua, Eduardo, Pascual, Consuelo, Pérez-Gonzalez, Rocio, Orive, Gorka, Carro, Eva
• Format: Journal Article
• Language: English
• Published: Netherlands 10.04.2015
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Administration, Intranasal; Animals; Cell Line, Tumor; Cell Survival - drug effects; Disease Models, Animal; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - immunology; Dopaminergic Neurons - pathology; Humans; Inflammation - drug therapy; Inflammation - immunology; Inflammation - pathology; Intercellular Signaling Peptides and Proteins - administration & dosage; Intercellular Signaling Peptides and Proteins - therapeutic use; Male; Mice; Mice, Inbred C57BL; NF-kappa B - immunology; Parkinson Disease, Secondary - drug therapy; Parkinson Disease, Secondary - immunology; Parkinson Disease, Secondary - pathology; Substantia Nigra - drug effects; Substantia Nigra - immunology; Substantia Nigra - pathology; Neuroprotection; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Inflammation; Parkinson's disease; Plasma rich in growth factors
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2015.02.030

Parkinson's disease is a common neurodegenerative disorder of unknown pathogenesis characterized by the loss of nigrostriatal dopaminergic neurons. Oxidative stress, microglial activation and inflammatory responses seem to contribute to the pathogenesis. Recent data showed that growth factors mediate neuroprotection in rodent models of Parkinson's disease, modulating pro-inflammatory processes. Based on our recent studies showing that plasma rich in growth factors (PRGF-Endoret) mediates neuroprotection as inflammatory moderator in Alzheimer's disease, in the present study we examined the effects of plasma rich in growth factors (PRGF-Endoret) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse as a translational therapeutic approach for Parkinson's disease. We found substantial neuroprotection by PRGF-Endoret in our model of Parkinson's disease, which resulted in diminished inflammatory responses and improved motor performance. Additionally, these effects were associated with robust reduction in nuclear transcription factor-κB (NF-κB) activation, and nitric oxide (NO), cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-α) expression in the substantia nigra. We propose that PRGF-Endoret can prevent dopaminergic degeneration via an NF-κB-dependent signaling process. As the clinical safety profile of PRGF-Endoret is already established, these data suggest that PRGF-Endoret provides a novel neuroprotective strategy for Parkinson's disease.