Sodium butyrate causes α-synuclein degradation by an Atg5-dependent and PI3K/Akt/mTOR-related autophagy pathway

Qiao, Chen-Meng; Sun, Mengfei; Jia, Xiaoyun; Shi, Yun; Zhang, Bo‐Ping; Zhou, Zhi-Lan; Zhao, Liping; Cui, Chun; Shen, Yan‐Qin

doi:10.1016/j.yexcr.2019.111772

Cited by 68 publications

(59 citation statements)

References 44 publications

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“…Lannucci and his coworkers proved that SCFAs induce autophagy in hepatic cells by uncoupling protein 2 (UCP2) [ 50 ]. Accordingly, Qiao et al demonstrated that sodium butyrate contributes to the reduction in α -synuclein both via the inhibition of the PI3K/Akt/mTOR autophagy pathway and enhancement of Atg5-mediated autophagy, manifested as elevated LC3II and reduced p62 expression [ 51 ].…”

Section: Mechanisms Underlying the Interaction Between Gut Microbimentioning

confidence: 99%

Implication of Gut Microbiota in Cardiovascular Diseases

Zhou

Cheng

Zhu

et al. 2020

Oxidative Medicine and Cellular Longevity

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Emerging evidence has identified the association between gut microbiota and various diseases, including cardiovascular diseases (CVDs). Altered intestinal flora composition has been described in detail in CVDs, such as hypertension, atherosclerosis, myocardial infarction, heart failure, and arrhythmia. In contrast, the importance of fermentation metabolites, such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and secondary bile acid (BA), has also been implicated in CVD development, prevention, treatment, and prognosis. The potential mechanisms are conventionally thought to involve immune regulation, host energy metabolism, and oxidative stress. However, numerous types of programmed cell death, including apoptosis, autophagy, pyroptosis, ferroptosis, and clockophagy, also serve as a key link in microbiome-host cross talk. In this review, we introduced and summarized the results from recent studies dealing with the relationship between gut microbiota and cardiac disorders, highlighting the role of programmed cell death. We hope to shed light on microbiota-targeted therapeutic strategies in CVD management.

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Section: Mechanisms Underlying the Interaction Between Gut Microbimentioning

confidence: 99%

Implication of Gut Microbiota in Cardiovascular Diseases

Zhou

Cheng

Zhu

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…In this regard, a few studies have shown beneficial effects of sodium butyrate in various animal models of PD (St Laurent et al 2013 ; Liu et al 2017a ; Funakohi-Tago et al 2018 ; Russo et al 2018 ; Srivastav et al 2019 ; Hou et al 2021 ), although at higher doses, this compound might aggravate the colonic inflammation in an MPTP mouse model (Qiao et al 2020a ). In vitro and in vivo studies have consistently found protective effects of sodium butyrate against dopaminergic cell damage brought about by alpha-synuclein (Paiva et al 2017 ; Qiao et al 2020b ). This protection is against both transcriptional deregulation and DNA damage (Paiva et al 2017 ).…”

Section: Butyratementioning

confidence: 99%

Novel Pharmacotherapies in Parkinson’s Disease

2021

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Parkinson’s disease (PD), an age-related progressive neurodegenerative condition, is associated with loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), which results in motor deficits characterized by the following: akinesia, rigidity, resting tremor, and postural instability, as well as nonmotor symptoms such as emotional changes, particularly depression, cognitive impairment, gastrointestinal, and autonomic dysfunction. The most common treatment for PD is focused on dopamine (DA) replacement (e.g., levodopa = L-Dopa), which unfortunately losses its efficacy over months or years and can induce severe dyskinesia. Hence, more efficacious interventions without such adverse effects are urgently needed. In this review, following a general description of PD, potential novel therapeutic interventions for this devastating disease are examined. Specifically, the focus is on nicotine and nicotinic cholinergic system, as well as butyrate, a short chain fatty acid (SCFA), and fatty acid receptors.

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“…Decreased fecal concentrations of SCFAs were detected in PD patients compared to healthy controls [ 283 ], in line with the observed reduction in SCFA-producing bacteria. Experimental studies further showed that oral administration of sodium butyrate attenuates behavioral and pathologic alterations in PD mice through amelioration of IEB integrity, inflammatory response and boosting neuronal autophagy [ 284 , 285 ]. However, other studies revealed that SCFAs may be deleterious in PD as they exacerbate PD phenotype in GF mice overexpressing α-syn [ 247 ].…”

Section: Roles Of Diet and Microbiota In Neurodegenerative Diseasementioning

confidence: 99%

Diet, Microbiota and Brain Health: Unraveling the Network Intersecting Metabolism and Neurodegeneration

Gentile

Doneddu

Riva

et al. 2020

IJMS

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Increasing evidence gives support for the idea that extra-neuronal factors may affect brain physiology and its predisposition to neurodegenerative diseases. Epidemiological and experimental studies show that nutrition and metabolic disorders such as obesity and type 2 diabetes increase the risk of Alzheimer’s and Parkinson’s diseases after midlife, while the relationship with amyotrophic lateral sclerosis is uncertain, but suggests a protective effect of features of metabolic syndrome. The microbiota has recently emerged as a novel factor engaging strong interactions with neurons and glia, deeply affecting their function and behavior in these diseases. In particular, recent evidence suggested that gut microbes are involved in the seeding of prion-like proteins and their spreading to the central nervous system. Here, we present a comprehensive review of the impact of metabolism, diet and microbiota in neurodegeneration, by affecting simultaneously several aspects of health regarding energy metabolism, immune system and neuronal function. Advancing technologies may allow researchers in the future to improve investigations in these fields, allowing the buildup of population-based preventive interventions and development of targeted therapeutics to halt progressive neurologic disability.

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Sodium butyrate causes α-synuclein degradation by an Atg5-dependent and PI3K/Akt/mTOR-related autophagy pathway

Cited by 68 publications

References 44 publications

Implication of Gut Microbiota in Cardiovascular Diseases

Implication of Gut Microbiota in Cardiovascular Diseases

Novel Pharmacotherapies in Parkinson’s Disease

Diet, Microbiota and Brain Health: Unraveling the Network Intersecting Metabolism and Neurodegeneration

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