Betaine Mitigates Amyloid-β-Associated Neuroinflammation by Suppressing the NLRP3 and NF-κB Signaling Pathways in Microglial Cells.

Abstract

BACKGROUND:

Microglia-driven neuroinflammation has been shown to be involved in the entire process of Alzheimer's disease (AD). Betaine is a natural product that exhibits anti-inflammatory activity; however, the exact underlying molecular mechanisms are poorly understood.

OBJECTIVE:

Our study focused on determining the effect of betaine against amyloid-β42 oligomer (AβO)-induced inflammation in microglial BV2 cells and investigating the underlying mechanism.

METHODS:

AβO was used to establish an in vitro AD model using BV2 cells. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay was used to measure BV2 cell viability with different concentrations of AβO and betaine. Reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assays were used to determine the expression levels of inflammatory factors, such as interleukin-1β (IL-1β), interleukin-18 (IL-18), and tumor necrosis factor α (TNF-α). Western blotting was used to evaluate the activation of the NOD-like receptor pyrin domain containing-3 (NLRP3) inflammasome and nuclear transcription factor-κB p65 (NF-κB p65). Moreover, we used phorbol 12-myristate 13-acetate (PMA) to activate NF-κB in order to validate that betaine exerted anti-neuroinflammatory effects through regulation of the NF-κB/NLRP3 signaling pathway.

RESULTS:

We used 2 mM betaine to treat 5μM AβO-induced microglial inflammation. The administration of betaine effectively decreased the levels of IL-1β, IL-18, and TNF-α without affecting cell viability in BV2 microglial cells.

CONCLUSION:

Betaine inhibited AβO-induced neuroinflammation in microglia by inhibiting the activation of the NLRP3 inflammasome and NF-κB, which supports further evaluation of betaine as a potential effective modulator for AD.

• Authors: Yue Zhang, Jianping Jia
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 94 Issue s1 Pg. S9-S19 ( 2023) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 37334594 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• NLR Family, Pyrin Domain-Containing 3 Protein
• Inflammasomes
• Interleukin-18
• Betaine
• Tumor Necrosis Factor-alpha
• Amyloid beta-Peptides

Topics

• Humans
• NF-kappa B (metabolism)
• Microglia (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Inflammasomes (metabolism)
• Interleukin-18 (metabolism)
• Betaine (pharmacology, metabolism)
• Neuroinflammatory Diseases
• Tumor Necrosis Factor-alpha (metabolism)
• Signal Transduction
• Inflammation (chemically induced, drug therapy, metabolism)
• Amyloid beta-Peptides (metabolism)