Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by amyloid-β plaque accumulation, tau tangles, and extensive neuroinflammation. Neuroinflammation, driven by glial cells like microglia and astrocytes, plays a critical role in AD progression. Initially, these cells provide protective functions, such as debris clearance and neurotrophic support. However, as AD progresses, chronic activation of these cells exacerbates inflammation, contributing to synaptic dysfunction, neuronal loss, and cognitive decline. Microglia release pro-inflammatory cytokines and reactive oxygen species (ROS), while astrocytes undergo reactive astrogliosis, further impairing neuronal health. This maladaptive response from glial cells significantly accelerates disease pathology. Current AD treatments primarily aim at symptomatic relief, with limited success in disease modification. While amyloid-targeting therapies like Aducanumab and Lecanemab show some promise, their efficacy remains limited. In this context, natural compounds have gained attention for their potential to modulate neuroinflammation and promote neuroprotection. Among these, butyrate and lauric acid are particularly notable. Butyrate, produced by a healthy gut microbiome, acts as a histone deacetylase (HDAC) inhibitor, reducing pro-inflammatory cytokines and supporting neuronal health. Lauric acid, on the other hand, enhances mitochondrial function, reduces oxidative stress, and modulates inflammatory pathways, thereby supporting glial and neuronal health. Both compounds have been shown to decrease amyloid-β deposition, reduce neuroinflammation, and promote neuroprotection in AD models. This review explores the mechanisms through which butyrate and lauric acid modulate glial and neuronal activity, highlighting their potential as therapeutic agents for mitigating neuroinflammation and slowing AD progression.
Document Type
Journal Article
Date of Publication
7-1-2025
Volume
17
Issue
14
Funding Information
Premium International / Edith Cowan University
School
School of Medical and Health Sciences
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Publisher
MDPI
Identifier
Rathnayaka Mudiyanselage Uththara Sachinthanie Senarath: https://orcid.org/0000-0003-4909-6296
Prashant Bharadwaj: https://orcid.org/0000-0003-4361-9906
Ralph N. Martins: https://orcid.org/0000-0002-4828-9363
Wanakulasuriya Mary Ann Dipika Binosha Fernando: https://orcid.org/0000-0002-8364-7808
Comments
Senarath, R. M. U. S., Oikari, L. E., Bharadwaj, P., Jayasena, V., Martins, R. N., & Fernando, W. M. a. D. B. (2025). The therapeutic potential of butyrate and lauric acid in modulating glial and neuronal activity in Alzheimer’s disease. Nutrients, 17(14), 2286. https://doi.org/10.3390/nu17142286