Sodium Butyrate Protects N2a Cells against A<i>β</i> Toxicity In Vitro

Sun, Jingxuan; Yuan, Boyu; Wu, Yanran; Gong, Yuhong; Guo, Wenjin; Fu, Shoupeng; Luan, Yongxin; Wang, Wei

doi:10.1155/2020/7605160

Cited by 32 publications

(17 citation statements)

References 60 publications

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“…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. Our previous studies also demonstrated that butyrate could exert neuroprotective effects on depression, PD, AD and traumatic brain injury in model mice (Liu et al, 2015;Sun et al, 2015Sun et al, , 2016aSun et al, ,b, 2020aLi et al, 2016).…”

Section: Metabolic Dysfunctionsmentioning

confidence: 97%

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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Section: Metabolic Dysfunctionsmentioning

confidence: 97%

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

Liu

Jiang

et al. 2021

Front. Aging Neurosci.

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“…The SCFAs propionic acid, butyric acid, and valeric acid were observed to inhibit the aggregation of both monomer Aβ 1-40 and Aβ 1-42 into Aβ oligomers and Aβ fibrils [ 130 ]. Moreover, sodium butyrate was shown to promote mitochondrial function and cell proliferation, which ameliorates Aβ-induced N2a cell damage [ 131 ]. In addition, sodium propionate showed a protective effect against Aβ-induced neurotoxicity by inhibiting the production of inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) [ 132 ].…”

Section: Scfas and Admentioning

confidence: 99%

“…In addition, sodium propionate showed a protective effect against Aβ-induced neurotoxicity by inhibiting the production of inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) [ 132 ]. In amyloidogenic APP processing, sodium butyrate can decrease the expression of APP and increase NEP expression levels [ 131 ]. However, sodium butyrate has also been shown to enhance neuronal apoptosis induced by the APP C-terminal fragment (C31, AICD, and C99) by lowering histone deacetylation to regulate gene transcription [ 133 ].…”

Section: Scfas and Admentioning

confidence: 99%

Mechanisms of Short-Chain Fatty Acids Derived from Gut Microbiota in Alzheimer's Disease

Qian¹,

Xie²,

Liu³

et al. 2022

Aging and disease

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Short-chain fatty acids (SCFAs) are important metabolites derived from the gut microbiota through fermentation of dietary fiber. SCFAs participate a number of physiological and pathological processes in the human body, such as host metabolism, immune regulation, appetite regulation. Recent studies on gut-brain interaction have shown that SCFAs are important mediators of gut-brain interactions and are involved in the occurrence and development of many neurodegenerative diseases, including Alzheimer's disease. This review summarizes the current research on the potential roles and mechanisms of SCFAs in AD. First, we introduce the metabolic distribution, specific receptors and signaling pathways of SCFAs in human body. The concentration levels of SCFAs in AD patient/animal models are then summarized. In addition, we illustrate the effects and mechanisms of SCFAs on the cognitive level, pathological features (Aβ and tau) and neuroinflammation in AD. Finally, we analyze the translational value of SCFAs as potential therapeutic targets for the treatment of AD.

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“…Although the mechanisms by which the gut microbiota contributes to brain health remain largely unknown, emerging data show that microbial metabolites are a possible link (Vogt et al, 2018 ; Fujii et al, 2019 ; Konjevod et al, 2020 ; Zhuang et al, 2021 ; Doifode et al, 2021 ). For example, short chain fatty acids (SCFAs, such as acetate, propionate, and butyrate) are the major beneficial metabolites produced by healthy microbiota; they exhibit beneficial effects on the brain, including a reduction in AD pathology, in several animal models (Mishra et al, 2020 ; Sun et al, 2020 ; Wenzel et al, 2020 ). Indeed, the abundance of SCFAs is often reduced in the gut of patients with AD and MCI, while healthy dietary habits, like a ketogenic diet, increase their production (Nagpal et al, 2019 , 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Activation of Microbiota Sensing – Free Fatty Acid Receptor 2 Signaling Ameliorates Amyloid-β Induced Neurotoxicity by Modulating Proteolysis-Senescence Axis

Razazan

Karunakar

Mishra

et al. 2021

Front. Aging Neurosci.

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Multiple emerging evidence indicates that the gut microbiota contributes to the pathology of Alzheimer’s disease (AD)—a debilitating public health problem in older adults. However, strategies to beneficially modulate gut microbiota and its sensing signaling pathways remain largely unknown. Here, we screened, validated, and established the agonists of free fatty acid receptor 2 (FFAR2) signaling, which senses beneficial signals from short chain fatty acids (SCFAs) produced by microbiota. The abundance of SCFAs, is often low in the gut of older adults with AD. We demonstrated that inhibition of FFAR2 signaling increases amyloid-beta (Aβ) stimulated neuronal toxicity. Thus, we screened FFAR2 agonists using an in-silico library of more than 144,000 natural compounds and selected 15 of them based on binding with FFAR2-agonist active sites. Fenchol (a natural compound commonly present in basil) was recognized as a potential FFAR2 stimulator in neuronal cells and demonstrated protective effects against Aβ-stimulated neurodegeneration in an FFAR2-dependent manner. In addition, Fenchol reduced AD-like phenotypes, such as Aβ-accumulation, and impaired chemotaxis behavior in Caenorhabditis (C.) elegans and mice models, by increasing Aβ-clearance via the promotion of proteolysis and reduced senescence in neuronal cells. These results suggest that the inhibition of FFAR2 signaling promotes Aβ-induced neurodegeneration, while the activation of FFAR2 by Fenchol ameliorates these abnormalities by promoting proteolytic Aβ-clearance and reducing cellular senescence. Thus, stimulation of FFAR2 signaling by Fenchol as a natural compound can be a therapeutic approach to ameliorate AD pathology.

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Sodium Butyrate Protects N2a Cells against Aβ Toxicity In Vitro

Cited by 32 publications

References 60 publications

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

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

Mechanisms of Short-Chain Fatty Acids Derived from Gut Microbiota in Alzheimer's Disease

Activation of Microbiota Sensing – Free Fatty Acid Receptor 2 Signaling Ameliorates Amyloid-β Induced Neurotoxicity by Modulating Proteolysis-Senescence Axis

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