{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:57:43Z","timestamp":1792119463731,"version":"4.4.0"},"reference-count":227,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a progressive neurodegenerative disorder marked by amyloid-\u03b2 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-\u03b2 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.<\/jats:p>","DOI":"10.3390\/nu17142286","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T15:36:58Z","timestamp":1752161818000},"page":"2286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The Therapeutic Potential of Butyrate and Lauric Acid in Modulating Glial and Neuronal Activity in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4909-6296","authenticated-orcid":false,"given":"Rathnayaka Mudiyanselage Uththara Sachinthanie","family":"Senarath","sequence":"first","affiliation":[{"name":"School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia"},{"name":"Australian Alzheimer\u2019s Research, Ralph and Patricia Sarich Neuroscience Research Institute, Nedlands, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotta E.","family":"Oikari","sequence":"additional","affiliation":[{"name":"Brain and Mental Health, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4361-9906","authenticated-orcid":false,"given":"Prashant","family":"Bharadwaj","sequence":"additional","affiliation":[{"name":"School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia"},{"name":"Australian Alzheimer\u2019s Research, Ralph and Patricia Sarich Neuroscience Research Institute, Nedlands, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Jayasena","sequence":"additional","affiliation":[{"name":"Nutrition and Food Science, School of Science, Western Sydney University, Campbelltown, NSW 2560, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph N.","family":"Martins","sequence":"additional","affiliation":[{"name":"School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia"},{"name":"Australian Alzheimer\u2019s Research, Ralph and Patricia Sarich Neuroscience Research Institute, Nedlands, WA 6009, Australia"},{"name":"Lions Alzheimer\u2019s Foundation, Nedlands, WA 6909, Australia"},{"name":"Department of Biomedical Sciences, Macquarie University, Sydney, NSW 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanakulasuriya Mary Ann Dipika Binosha","family":"Fernando","sequence":"additional","affiliation":[{"name":"School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia"},{"name":"Australian Alzheimer\u2019s Research, Ralph and Patricia Sarich Neuroscience Research Institute, Nedlands, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"ref_1","first-page":"a006189","article-title":"Neuropathological Alterations in Alzheimer Disease","volume":"1","author":"Frosch","year":"2011","journal-title":"Cold Spring Harb. 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