2026-09-15T15:03:19Zhttps://gredos.usal.es/oai/request

oai:gredos.usal.es:10366/1686752026-01-14T01:02:57Zcom_10366_4613com_10366_4576com_10366_3823col_10366_4615

00925njm 22002777a 4500 dc Pérez Revuelta, Laura author Pérez Boyero, David author Pérez Martín, Ester author Lorena Cabedo, Valeria author González Téllez de Meneses, Pablo author Weruaga Prieto, Eduardo author Díaz López, David author Alonso Peña, José Ramón author 2025-01-10 [EN] In recent decades, the scientific community has faced a major challenge in the search for new therapies that can slow down or alleviate the process of neuronal death that accompanies neurodegenerative diseases. This study aimed to identify an effective therapy using neurotrophic factors to delay the rapid and aggressive cerebellar degeneration experienced by the Purkinje Cell Degeneration (PCD) mouse, a model of childhood-onset neurodegeneration with cerebellar atrophy (CONDCA). Initially, we analyzed the changes in the expression of several neurotrophic factors related to the degenerative process itself, identifying changes in insulin-like growth factor 1 (IGF-1) and Vascular Endothelial Growth Factor B (VEGF-B) in the affected animals. Then, we administered pharmacological treatments using human recombinant IGF-1 (rhIGF-1) or VEGF-B (rhVEGF-B) proteins, considering their temporal variations during the degenerative process. The effects of these treatments on motor, cognitive, and social behavior, as well as on cerebellar destructuration were analyzed. Whereas treatment with rhIGF-1 did not demonstrate any neuroprotective effect, rhVEGF-B administration at moderate dosages stopped the process of neuronal death and restored motor, cognitive, and social functions altered in PCD mice (and CONDCA patients). However, increasing the frequency of rhVEGF-B administration had a detrimental effect on Purkinje cell survival, suggesting an inverted U-shaped dose-response curve of this substance. Additionally, we demonstrate that this neuroprotective effect was achieved through a partial inhibition or delay of apoptosis. These findings provide strong evidence supporting the use of rhVEGF-B as a pharmacological agent to limit severe cerebellar neurodegenerative processes. Pérez-Revuelta, L., Pérez-Boyero, D., Pérez-Martín, E., Cabedo, V. L., Téllez De Meneses, P. G., Weruaga, E., Díaz, D., y Alonso, J. R. (2025). Neuroprotective effects of vegf-b in a murine model of aggressive neuronal loss with childhood onset. International Journal of Molecular Sciences, 26(2), 538. https://doi.org/10.3390/ijms26020538 1661-6596 http://hdl.handle.net/10366/168675 10.3390/ijms26020538 39859255 1422-0067 Neurodegeneration Neurotherapeutics PCD mouse Cerebellum Purkinje cells Neurotrophic factors Neuroprotective Effects of VEGF-B in a Murine Model of Aggressive Neuronal Loss with Childhood Onset.