H3K27 acetylation-induced FSTL1 upregulation by P300/RUNX1 co-activation exacerbated autophagy-mediated neuronal damage and NF-κB-stimulated inflammation in Alzheimer's disease.

Abstract

Follistatin-like protein 1 (FSTL1) has been demonstrated to participate in the pathogenesis of several neurological diseases. The current study informed the role of H3K27 acetylation-induced FSTL1 upregulation in Alzheimer's disease (AD). Our investigation discovered the upregulated FSTL1 expression and enhanced autophagy activity in AD. FSTL1 knockdown successfully attenuated the injuries of Aβ_1-42-challenged SH-SY5Y cells through the inhibition of autophagy activity. Besides, FSTL1 deficiency suppresses the inflammatory response and NF-κB signaling in AD. Moreover, it was found that p300 was recruited by transcriptional factor RUNX1 to stimulate the H3K27 acetylation in FSTL1 promoter region, which caused the upregulation of FSTL1 in AD. To summarize, p300 acted as a co-activator of RUNX1 to trigger the activation of FSTL1 in AD, resulting in the exacerbated injuries and inflammatory responses of Aβ_1-42-induced SH-SY5Y cells.