School of Medicine
Activity of neprilysin (NEP), the major protease which cleaves amyloid-β peptide (Aβ), is reportedly reduced in the brains of patients with Alzheimer’s disease (AD). Accumulation of Aβ generates reactive oxygen species (ROS) such as 4-hydroxynonenal (HNE), and then reduces activities of Aβ-degrading enzymes including NEP. Xanthorrhizol (Xan), a natural sesquiterpenoid, has been reported to possess antioxidant and anti-inflammatory proper- ties. The present study examined the effects of Xan on HNE- or oligomeric Aβ42-induced ox- idative modification of NEP protein. Xan was added to the HNE- or oligomeric Aβ42-treated SK-N-SH human neuroblastoma cells and then levels, oxidative modification and enzymatic activities of NEP protein were measured. Increased HNE levels on NEP proteins and re- duced enzymatic activities of NEP were observed in the HNE- or oligomeric Aβ42-treated cells. Xan reduced HNE levels on NEP proteins and preserved enzymatic activities of NEP in HNE- or oligomeric Aβ42-treated cells. Xan reduced Aβ42 accumulation and protected neurones against oligomeric Aβ42-induced neurotoxicity through preservation of NEP ac- tivities. These findings indicate that Xan possesses therapeutic potential for the treatment of neurodegenerative diseases, including AD, and suggest a potential mechanism for the neuroprotective effects of antioxidants for the prevention of AD.
Digital Commons Citation
Lim, Chol Seung and Han, Jung-Soo, "The antioxidant xanthorrhizol prevents amyloid-β-induced oxidative modification and inactivation of neprilysin" (2018). Faculty & Staff Scholarship. 1821.
Lim, C. S., & Han, J.-S. (2018). The antioxidant xanthorrhizol prevents amyloid-β-induced oxidative modification and inactivation of neprilysin. Bioscience Reports, 38(1). https://doi.org/10.1042/bsr20171611