1. Academic Validation
  2. Evidence for TGF-β1/Nrf2 Signaling Crosstalk in a Cuprizone Model of Multiple Sclerosis

Evidence for TGF-β1/Nrf2 Signaling Crosstalk in a Cuprizone Model of Multiple Sclerosis

  • Antioxidants (Basel). 2024 Jul 29;13(8):914. doi: 10.3390/antiox13080914.
Coram Guevara 1 Sinay C Vicencio 1 Ignacio S Pizarro 1 Francisca Villavicencio-Tejo 2 Rodrigo A Quintanilla 2 Pablo Astudillo 3 Estibaliz Ampuero 4 Rodrigo Varas 5 Juan A Orellana 6 7 Fernando C Ortiz 1
Affiliations

Affiliations

  • 1 Mechanisms of Myelin Formation and Repair Laboratory, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170022, Chile.
  • 2 Laboratory of Neurodegenerative Diseases, Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago 8910060, Chile.
  • 3 Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago 8910060, Chile.
  • 4 Laboratorio Neurofarmacología del Comportamiento, Facultad de Química y Biología, Universidad de Santiago, Santiago9170022, Chile.
  • 5 Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago 8910060, Chile.
  • 6 Departamento de Neurología, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile.
  • 7 Centro Interdisciplinario de Neurociencias, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile.
Abstract

Multiple sclerosis (MS) is a chronic and degenerative disease that impacts central nervous system (CNS) function. One of the major characteristics of the disease is the presence of regions lacking myelin and an oxidative and inflammatory environment. TGF-β1 and Nrf2 proteins play a fundamental role in different oxidative/inflammatory processes linked to neurodegenerative diseases such as MS. The evidence from different experimental settings has demonstrated a TGF-β1-Nrf2 signaling crosstalk under pathological conditions. However, this possibility has not been explored in experimental models of MS. Here, by using the cuprizone-induced demyelination model of MS, we report that the in vivo pharmacological blockage of the TGF-β1 receptor reduced Nrf2, catalase, and TGFβ-1 protein levels in the demyelination phase of cuprizone administration. In addition, ATP production, locomotor function and cognitive performance were diminished by the treatment. Altogether, our results provide evidence for a crosstalk between TGF-β1 and Nrf2 signaling pathways under CNS demyelination, highlighting the importance of the antioxidant cellular response of neurodegenerative diseases such as MS.

Keywords

Nrf2; demyelination; multiple sclerosis; neuroinflammation; oxidative stress; transforming growth factor β1 TGF-β1.

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