IMR Press / JIN / Volume 19 / Issue 3 / DOI: 10.31083/j.jin.2020.03.112
Open Access Original Research
Muramyl dipeptide promotes Aβ1-42 oligomer production via the nod2/p-p38 mapk/bace1 signaling pathway in the sh-sy5y cells
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1 Geriatrics Department of Chinese Medicine, Huadong Hospital, Fudan University, Shanghai, 200040, P. R. China
2 Geriatrics Department of Chinese Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, P. R. China
3 Department of Chinese Medicine, East Hospital, Tongji University, Shanghai, 310000, P. R. China
*Correspondence: doctorymli@163.com (Ya-Ming Li); cyzhang0810@163.com (Chun-Yan Zhang)
J. Integr. Neurosci. 2020, 19(3), 421–428; https://doi.org/10.31083/j.jin.2020.03.112
Submitted: 22 April 2020 | Revised: 12 July 2020 | Accepted: 14 July 2020 | Published: 30 September 2020
Copyright: © 2020 Chen et al. Published by IMR Press.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
Abstract

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.

Keywords
Alzheimer’s disease
Muramyl dipeptide
Nucleotide-binding oligomerization domain 2
β-site APP cleaving enzyme 1
Aβ1-42 oligomer
Figures
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