The Link between Gut Dysbiosis and Neuroinflammation in Parkinson’s Disease

Baizabal‐Carvallo, José Fidel; Alonso-Juárez, Marlene

doi:10.1016/j.neuroscience.2020.02.030

Cited by 92 publications

(65 citation statements)

References 141 publications

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“…Furthermore, metabolic products synthesized by the microbiota when crossing the BBB trigger the inflammatory cascade, including microglial activation and neuronal dysfunction leading to the death of neurons. More recently, previous studies conducted with PD patients have shown evidence of an altered intestinal microbiota, systemically releasing endotoxins such as lipopolysaccharides and metabolic products facilitating their entry into the CNS promoting the activation of the microglia inducing inflammatory responses, such as the release of pro-inflammatory cytokines (IL1-α, IL-β, IL-6 and TNF-α), leading to the degeneration of dopaminergic neurons [66,67]. Therefore, due to the anti-inflammatory properties exhibited by Loliolide, as well as its ability to cross the BBB as described by Ahmed et al [68], its application as a dietary anti-inflammatory molecule can represent an excellent strategy to contribute for PD therapeutics.…”

Section: Discussionmentioning

confidence: 99%

Loliolide, a New Therapeutic Option for Neurological Diseases? In Vitro Neuroprotective and Anti-Inflammatory Activities of a Monoterpenoid Lactone Isolated from Codium tomentosum

Silva

Alves

Martins

et al. 2021

IJMS

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Parkinsons Disease (PD) is the second most common neurodegenerative disease worldwide, and is characterized by a progressive degeneration of dopaminergic neurons. Without an effective treatment, it is crucial to find new therapeutic options to fight the neurodegenerative process, which may arise from marine resources. Accordingly, the goal of the present work was to evaluate the ability of the monoterpenoid lactone Loliolide, isolated from the green seaweed Codium tomentosum, to prevent neurological cell death mediated by the neurotoxin 6-hydroxydopamine (6-OHDA) on SH-SY5Y cells and their anti-inflammatory effects in RAW 264.7 macrophages. Loliolide was obtained from the diethyl ether extract, purified through column chromatography and identified by NMR spectroscopy. The neuroprotective effects were evaluated by the MTT method. Cells´ exposure to 6-OHDA in the presence of Loliolide led to an increase of cells´ viability in 40%, and this effect was mediated by mitochondrial protection, reduction of oxidative stress condition and apoptosis, and inhibition of the NF-kB pathway. Additionally, Loliolide also suppressed nitric oxide production and inhibited the production of TNF-α and IL-6 pro-inflammatory cytokines. The results suggest that Loliolide can inspire the development of new neuroprotective therapeutic agents and thus, more detailed studies should be considered to validate its pharmacological potential.

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Section: Discussionmentioning

confidence: 99%

Loliolide, a New Therapeutic Option for Neurological Diseases? In Vitro Neuroprotective and Anti-Inflammatory Activities of a Monoterpenoid Lactone Isolated from Codium tomentosum

Silva

Alves

Martins

et al. 2021

IJMS

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“…Butyrate is a short-chain fatty acid (SCFA) that is produced by gut microbiota and acts primarily as an energy source for colonic epithelial cells and has been shown to have anti-inflammatory, enteroendocrine and epigenetic effects that not only influences colonic and systemic health but can also affect the brain function (Cantu-Jungles et al, 2019 ). Recent advances in our understanding of the gut-brain axis has resulted in new insights and potential novel targets for therapeutic intervention in PD (Baizabal-Carvallo and Alonso-Juarez, 2020 ; Cirstea et al 2020 ; Cryan et al 2020 ). Indeed, it has been suggested that the initiation and progression of PD may be impeded through manipulation of the gut microbiota.…”

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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“…It was noted that multiple gastrointestinal (GI) abnormalities including weight loss, dysphagia, and constipation always precede motor-symptoms by many years as common PD manifestations (Verbaan et al, 2007), suggesting the linkage between the PD pathogenesis and GI dysfunctions of involving gut microbial imbalance (Kim et al, 2015). Recent reported works demonstrated the crucial role of gut microbial dysbiosis induced imbalance of the gut-microbiome-brain axis in pathogenesis and development of PD (Baizabal-Carvallo et al, 2020). To date, evidences are still being accumulated and increasing works are still under conducting to elucidate the interactions between microbiota-gut-brain axis and PD pathology.…”

Section: Introductionmentioning

confidence: 99%

Chicoric acid prevents neurodegeneration via microbiota-gut-brain axis in a mouse Parkinson’s disease model

Qian

Wang

et al. 2021

Preprint

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It is determined that microbiota-gut-brain axis is involved in the pathogenesis of Parkinson's Disease (PD) and may be the potential target for developing the therapeutic treatments for PD. Chicoric acid (CA) is a kind of natural polyphenolic acid compounds which are recognized as promising agents against neurodegenerative disease. Here, we investigated the influence of CA on microbiota-gut-brain axis in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mice. The results demonstrated that oral pretreatments of CA significantly prevented the MPTP-indued motor disorders, death of nigrostriatal dopaminergic neurons and reduction in striatal neurotrophins. Sequencing results of 16S rRNA indicated the microbial dysbiosis occurred in MPTP mice, whereas CA exerted a remarkable impact on microbial diversity and microbiota compositions, as well as SCFAs production. Besides, CA pretreatment alleviated gliosis-mediated neuroinflammation and gut inflammation by suppressing TLR4/MyD88/NF-?5;B signaling cascade, along with preventing the colonic hyperpermeability. To conclude, CA prevented MPTP-induced neuroinflammation and neuronal degenerative processes through signaling multiple pathways of microbiota-gut-brain axis.

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The Link between Gut Dysbiosis and Neuroinflammation in Parkinson’s Disease

Cited by 92 publications

References 141 publications

Loliolide, a New Therapeutic Option for Neurological Diseases? In Vitro Neuroprotective and Anti-Inflammatory Activities of a Monoterpenoid Lactone Isolated from Codium tomentosum

Loliolide, a New Therapeutic Option for Neurological Diseases? In Vitro Neuroprotective and Anti-Inflammatory Activities of a Monoterpenoid Lactone Isolated from Codium tomentosum

Novel Pharmacotherapies in Parkinson’s Disease

Chicoric acid prevents neurodegeneration via microbiota-gut-brain axis in a mouse Parkinson’s disease model

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