Muramyl dipeptide promotes Aβ1-42 oligomer production via the NOD2/p-p38 MAPK/BACE1 signaling pathway in the SH-SY5Y cells

• Main Author: Yan-Jie Chen, Yuan-Jin Chan, Wen-Jing Chen, Ya-Ming Li, Chun-Yan Zhang
• Format: Article
• Language: English
• Published: IMR (Innovative Medical Research) Press Limited 2020-09-01
• Series: Journal of Integrative Neuroscience
• Subjects: |alzheimer’s disease|muramyl dipeptide|nucleotide-binding oligomerization domain 2|β-site app cleaving enzyme 1|aβ1-42 oligomer
• Online Access: https://jin.imrpress.com/fileup/1757-448X/PDF/1601430238448-990650090.pdf

The relationship between chronic bacterial colonization in the brain and Alzheimer’s disease is attracting extensive attention. Recent studies indicated that the components of bacterial biofilm drive the amyloid-β production. Muramyl dipeptide, the minimal bioactive peptidoglycan motif common to all bacteria, contributes to the development of many central inflammatory and neurodegenerative disorders. However, the involvement of Muramyl dipeptide in amyloid-β production is not completely defined. In our present study, wild type mice received an intracerebroventricular injection of normal saline or Muramyl dipeptide. Data showed that the production of Aβ1-42 oligomers was significantly increased after Muramyl dipeptide injection in the wild type mice or incubation of the SH-SY5Y cells with Muramyl dipeptide. Moreover, the action of Muramyl dipeptide was dose- and time-dependent. The above results suggested a possibility that the Muramyl dipeptide -induced Aβ1-42 oligomer production might be related to the NOD2/p-p38 MAPK/BACE1 pathway. To confirm this, the SH-SY5Y cells were transfected with siRNA NOD2. Data showed that the transfected SH-SY5Y cells exhibited decreased expression of Aβ1-42 oligomer, NOD2, p-p38 MAPK, and BACE1 after treatment with Muramyl dipeptide. Finally, SH-SY5Y cells were pretreated with SB203580, an inhibitor of the p-38-MAPK pathway. The results indicated that these pretreated SH-SY5Y cells exhibited decreased expression of Aβ1-42 oligomer, p-p38 MAPK, and BACE1 after treatment with Muramyl dipeptide. In conclusion, these results suggested that Muramyl dipeptide was the trigger factor for Aβ1-42 oligomer production, which probably acts via the NOD2/p-p38 MAPK/BACE1 signaling pathway.