Inhibition of tau phosphorylation and Aβ accumulation by S. cerevisiae-derived vacuoles in LPS-induced SH-SY5Y cells

Ngoc-Han Thi Nguyen; Ji Hun Kim; Su-Min Lee; Byung-Kwan Cho; Yang-Hoon Kim; Jiho Min

doi:10.1016/j.jbiotec.2023.09.005

Inhibition of tau phosphorylation and Aβ accumulation by S. cerevisiae-derived vacuoles in LPS-induced SH-SY5Y cells

J Biotechnol. 2023 Nov 10:376:45-52. doi: 10.1016/j.jbiotec.2023.09.005. Epub 2023 Sep 28.

Authors

Ngoc-Han Thi Nguyen¹, Ji Hun Kim², Su-Min Lee³, Byung-Kwan Cho⁴, Yang-Hoon Kim⁵, Jiho Min⁶

Affiliations

¹ School of Chemical Engineering, Jeonbuk National University, 567 Baekje-daero, Deokjin-Gu, Jeonju 54896, South Korea.
² Department of Biological Sciences, Korea Advanced institute of Science and Technology, 291 Daehak-ro, Yuseong-Gu, Daejeon 34141, South Korea.
³ Graduate School of Semiconductor and Chemical Engineering, Jeonbuk National University, 567 Baekje-daero, Deokjin-Gu, Jeonju 54896, South Korea.
⁴ Department of Biological Sciences, Korea Advanced institute of Science and Technology, 291 Daehak-ro, Yuseong-Gu, Daejeon 34141, South Korea. Electronic address: bcho@kaist.ac.kr.
⁵ School of Biological Sciences, Chungbuk National University, 1 Chungdae-Ro, Seowon-Gu, Cheongju 28644, South Korea. Electronic address: kyh@chungbuk.ac.kr.
⁶ School of Chemical Engineering, Jeonbuk National University, 567 Baekje-daero, Deokjin-Gu, Jeonju 54896, South Korea; Graduate School of Semiconductor and Chemical Engineering, Jeonbuk National University, 567 Baekje-daero, Deokjin-Gu, Jeonju 54896, South Korea. Electronic address: jihomin@jbnu.ac.kr.

PMID: 37777088
DOI: 10.1016/j.jbiotec.2023.09.005

Abstract

Neurodegenerative diseases, such as Alzheimer's disease (AD), are characterized by the accumulation of intracellular tau and amyloid beta (Aβ) proteins, which lead to neuroinflammation and neuronal apoptosis. In this study, we investigated the potential of a bioengineered vacuoles derived from Saccharomyces cerevisiae-derived vacuoles to treat neuroinflammation and protein accumulation in AD. The yeast-derived vacuole is a small organelle that achieves efficient degradation by utilizing a diverse array of hydrolytic enzymes. These hydrolytic enzymes break down and process proteins into smaller fragments. We found that vacuoles treatment significantly reduced LPS-primed cell apoptosis and diminished Aβ42 secretion in vitro, potentially through the inhibition of the NF-kB p65 signaling pathway. Additionally, vacuole pre-treatment down-regulated NF-κB translocation and reduced phosphorylated tau levels in LPS-induced SH-SY5Y cells. Our results suggest that the vacuoles have potential as a therapeutic agent for neurodegenerative diseases. The vacuole's small size and diverse hydrolytic enzymes make it a promising drug delivery system for targeting intracellular proteins. Future studies may explore the use of vacuoles in animal models of AD to determine their therapeutic potential.

Keywords: NF-kB signaling pathway: Tau protein; Neurodegeneration; Neuroinflammation; S. cerevisiae-derived vacuoles; SH-SY5Y cells.