@article{10902/37475,
year = {2025},
url = {https://hdl.handle.net/10902/37475},
abstract = {SQSTM1/p62 has an essential role in autophagy, a catabolic pathway that is vital for maintaining cell homeostasis. p62 alterations have been observed in multiple pathological conditions, including neurodegenerative diseases and bone metabolism alterations. The p.R321C p62 protein mutation has been described in patients with amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Paget's disease of bone. In vitro studies associated the p62-321C variant with a blockade of autophagy and with the activation of the NF-kB pathway. We aimed to provide a deeper understating of the pathophysiological consequences of the p.R321C p62 mutation using a humanized mouse model. Micro-computed tomography, immunohistochemistry, and western blot analysis studied the functional consequences of the p. R321C p62 mutation. Statistical analyses were performed using SPSS software. The results showed that the p62-321C mice developed seizures after tactile-vestibular stimulation, probably associated with a blockage of the autophagy and NF-kB activation. Changes in expression of cFos and p62 were found in the amygdala, hypothalamic nuclei, and hippocampi nuclei. In addition, numerous degenerating motor neurons were observed in the spinal cord of the p62-321C mice. We report that the blockage of the autophagy, caused by p.R321C p62 mutation, is associated with abnormalities in the central nervous system, mainly seizures after tactile-vestibular stimulation and degeneration of the motor neurons of the spinal cord but not with bone abnormalities in a humanized mouse model.},
organization = {This work was funded by Projects ISC IIII-FEDER: PI16/01920 and PI20/01589 from Instituto de Salud Carlos
III (Ministry of Science and Innovation).},
publisher = {Scientific Reports, 2025, 15(1), 16929},
title = {The p.R321C mutation in the p62 protein is associated with abnormalities in the central nervous system},
author = {Usategui Martín, Ricardo and Esteban López, Vega and Chantre Fortes, Estefanía and Sánchez Martín, Manuel and Riancho Moral, José Antonio and López, Dolores E. and González Sarmiento, Rogelio},
}