Sodium Butyrate Reduces Brain Amyloid-β Levels and Improves Cognitive Memory Performance in an Alzheimer’s Disease Transgenic Mouse Model at an Early Disease Stage

Fernando, Warnakulasuriya Mary Ann Dipika Binosha; Martins, Ian; Morici, Michael; Bharadwaj, Prashant; Rainey-Smith, Stephanie R.; Lim, Wei Ling Florence; Martins, Ralph N.

doi:10.3233/jad-190120

Cited by 85 publications

(58 citation statements)

References 50 publications

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“…AD is a complex multifactorial pathology. Aβ exhibited neurotoxicity and contributed to neuronal death, which was thought to be the primary factor in initiating the pathogenesis of AD [39,40]. Several neurotoxic effects of Aβ shown in the present study are consistent with previous studies [41,42].…”

Section: Compound 5c Inhibited Expression Of Rage Of Aβ 25-35 -Inducesupporting

confidence: 92%

Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on β-Amyloid-Induced PC12 Cells

Liu

Bian

et al. 2020

Molecules

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A series of novel synthetic substituted benzo[d]oxazole-based derivatives (5a–5v) exerted neuroprotective effects on β-amyloid (Aβ)-induced PC12 cells as a potential approach for the treatment of Alzheimer’s disease (AD). In vitro studies show that most of the synthesized compounds were potent in reducing the neurotoxicity of Aβ25-35-induced PC12 cells at 5 μg/mL. We found that compound 5c was non-neurotoxic at 30 μg/mL and significantly increased the viability of Aβ25-35-induced PC12 cells at 1.25, 2.5 and 5 μg/mL. Western blot analysis showed that compound 5c promoted the phosphorylation of Akt and glycogen synthase kinase (GSK-3β) and decreased the expression of nuclear factor-κB (NF-κB) in Aβ25-35-induced PC12 cells. In addition, our findings demonstrated that compound 5c protected PC12 cells from Aβ25-35-induced apoptosis and reduced the hyperphosphorylation of tau protein, and decreased the expression of receptor for AGE (RAGE), β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), inducible nitric oxide synthase (iNOS) and Bcl-2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-2) via Akt/GSK-3β/NF-κB signaling pathway. In vivo studies suggest that compound 5c shows less toxicity than donepezil in the heart and nervous system of zebrafish.

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Section: Compound 5c Inhibited Expression Of Rage Of Aβ 25-35 -Inducesupporting

confidence: 92%

Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on β-Amyloid-Induced PC12 Cells

Liu

Bian

et al. 2020

Molecules

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“…Butyrate is a multifunctional molecule that exerts beneficial neuroprotective effects and improves brain health. Butyrate can also interfere with Aβ1-40 oligomerization and exert multiple effects against neuropsychiatric disorders as an inhibitor of HDAC, which can improve cognitive memory performance in a 5 × FAD mouse at an early disease stage (Griseri et al, 2003;Ho et al, 2018;Fernando et al, 2020). Sun et al (2020b) found that butyrate protects N2a cells from Aβ-induced cell damage by activating GPR109A in vitro.…”

Section: Metabolic Dysfunctionsmentioning

confidence: 99%

Roles and Mechanisms of Gut Microbiota in Patients With Alzheimer’s Disease

Liu

Jiang

et al. 2021

Front. Aging Neurosci.

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Alzheimer’s disease (AD) is the most common age-related progressive neurodegenerative disease, characterized by a decline in cognitive function and neuronal loss, and is caused by several factors. Numerous clinical and experimental studies have suggested the involvement of gut microbiota dysbiosis in patients with AD. The altered gut microbiota can influence brain function and behavior through the microbiota–gut–brain axis via various pathways such as increased amyloid-β deposits and tau phosphorylation, neuroinflammation, metabolic dysfunctions, and chronic oxidative stress. With no current effective therapy to cure AD, gut microbiota modulation may be a promising therapeutic option to prevent or delay the onset of AD or counteract its progression. Our present review summarizes the alterations in the gut microbiota in patients with AD, the pathogenetic roles and mechanisms of gut microbiota in AD, and gut microbiota–targeted therapies for AD. Understanding the roles and mechanisms between gut microbiota and AD will help decipher the pathogenesis of AD from novel perspectives and shed light on novel therapeutic strategies for AD.

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“…In 5XFAD mice, butyrate both decreased Aβ deposition and improved cognition. Here, the effect of the treatment in an early disease stage was examined ( 148 ), suggesting that the effect of butyrate on Aβ deposition might be dependent on disease stage. Additionally, treatment of APP/PS1 mice with Clostridium butyricum increased fecal butyrate concentrations and ameliorated cognitive deficits and neurodegeneration, suppressed microglia activation and decreased levels of the pro-inflammatory cytokines Il-1β and TNF-α.…”

Section: Therapeutic Strategies Targeting the Gut Microbiota And Metabolites In Admentioning

confidence: 99%

Contribution of Gut Microbiota to Immunological Changes in Alzheimer’s Disease

et al. 2021

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Emerging evidence suggests that both central and peripheral immunological processes play an important role in the pathogenesis of Alzheimer’s disease (AD), but regulatory mechanisms remain unknown. The gut microbiota and its key metabolites are known to affect neuroinflammation by modulating the activity of peripheral and brain-resident immune cells, yet an overview on how the gut microbiota contribute to immunological alterations in AD is lacking. In this review, we discuss current literature on microbiota composition in AD patients and relevant animal models. Next, we highlight how microbiota and their metabolites may contribute to peripheral and central immunological changes in AD. Finally, we offer a future perspective on the translation of these findings into clinical practice by targeting gut microbiota to modulate inflammation in AD. Since we find that gut microbiota alterations in AD can induce peripheral and central immunological changes via the release of microbial metabolites, we propose that modulating their composition may alter ongoing inflammation and could therefore be a promising future strategy to fight progression of AD.

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Sodium Butyrate Reduces Brain Amyloid-β Levels and Improves Cognitive Memory Performance in an Alzheimer’s Disease Transgenic Mouse Model at an Early Disease Stage

Cited by 85 publications

References 50 publications

Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on β-Amyloid-Induced PC12 Cells

Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on β-Amyloid-Induced PC12 Cells

Roles and Mechanisms of Gut Microbiota in Patients With Alzheimer’s Disease

Contribution of Gut Microbiota to Immunological Changes in Alzheimer’s Disease

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