Early Growth Response Gene-1 Deficiency Interrupts TGF β1 Signaling Activation and Aggravates Neurodegeneration in Experimental Autoimmune Encephalomyelitis Mice

This study demonstrated that Egr-1 was down-regulated at mRNA and protein levels in the central nervous system (CNS) of experimental autoimmune encephalomyelitis (EAE) mice. Egr-1 knockout exacerbated EAE progression in mice, as shown by increased disease severity and incidence; it also aggravated neuronal apoptosis, which was associated with weakened activation of the BDNF/TGF β 1/MAPK/Akt signaling pathways in the CNS of EAE mice. Consistently, Egr-1 siRNA promoted apoptosis but mitigated the activation of BDNF/TGFβ 1/MAPK/Akt signaling in SH-SY5Y cells. Our results revealed that Egr-1 is a crucial regulator of neuronal survival in EAE by regulating TGFβ 1-mediated si gnaling activation, implicating the important role of Egr-1 in the pathogenesis of multiple sclerosis as a potential novel therapy target.
Source: Neuroscience Bulletin - Category: Neuroscience Source Type: research