Role of melatonin in TLR4-mediated inflammatory pathway in the MTPT-induced mouse model

Yıldırım, Sendegül; Özkan, Ayşe; Aytaç, Güneş; Ağar, Ayşel; Tanrıöver, Gamze

doi:10.1016/j.neuro.2021.11.011

Cited by 15 publications

(11 citation statements)

References 81 publications

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“…The main toxic component of Lewy bodies is the protein a-synuclein which plays a pivotal role in PD pathogenesis. There are several key molecular pathogenic mechanisms-including genetic factors, a-synuclein aggregation, impairment of protein clearance, mitochondrial dysfunction, ferroptosis, neuroinflammation, and oxidative stress-involved in PD pathogenesis (11)(12)(13). The exact PD pathogenesis is yet to be completely elucidated owing to the multifactorial nature of the disease, leading to the lack of disease-modifying treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota: A Novel Therapeutic Target for Parkinson’s Disease

Zhu

Liu

et al. 2022

Front. Immunol.

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Parkinson’s disease (PD) is the second most common neurodegenerative disease characterized by motor dysfunction. Growing evidence has demonstrated that gut dysbiosis is involved in the occurrence, development and progression of PD. Numerous clinical trials have identified the characteristics of the changed gut microbiota profiles, and preclinical studies in PD animal models have indicated that gut dysbiosis can influence the progression and onset of PD via increasing intestinal permeability, aggravating neuroinflammation, aggregating abnormal levels of α-synuclein fibrils, increasing oxidative stress, and decreasing neurotransmitter production. The gut microbiota can be considered promising diagnostic and therapeutic targets for PD, which can be regulated by probiotics, psychobiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, diet modifications, and Chinese medicine. This review summarizes the recent studies in PD-associated gut microbiota profiles and functions, the potential roles, and mechanisms of gut microbiota in PD, and gut microbiota-targeted interventions for PD. Deciphering the underlying roles and mechanisms of the PD-associated gut microbiota will help interpret the pathogenesis of PD from new perspectives and elucidate novel therapeutic strategies for PD.

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Section: Introductionmentioning

confidence: 99%

Gut Microbiota: A Novel Therapeutic Target for Parkinson’s Disease

Zhu

Liu

et al. 2022

Front. Immunol.

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“…As an age-related hormone, MLT has been reported with broad biological effects including immunity-regulation 17 . MLT has been proved to protect tyrosine hydroxylase (TH) positive neurons (DA neurons) by reducing neuroinflammation in mouse SN C and having a positive effect on the motor function of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model 18 . However, specific neuroprotective mechanisms of MLT in PD, that is, whether MLT inhibits neuroinflammation and its underlying mechanisms, remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Melatonin ameliorates Parkinson’s disease via regulating microglia polarization in a RORα‐dependent pathway

Liu

Wang

et al. 2022

npj Parkinsons Dis.

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An important pathophysiological component of Parkinson’s Disease (PD) is circadian rhythm disorder, closely related to a decrease in circulated melatonin (MLT) level. It has been reported recently that retinoic acid-associated orphan nuclear receptor (RORα), for the potentiallyendogenous ligand MLT, plays an important role in various diseases. However, the function of RORα in the pathogenesis of neurodegenerative diseases remains much unclear. Here, we showed in a cellular PD model that RORα expression was down-regulated in 1 methyl 4 phenyl pyridinium ion (MPP+)-treated BV2 cells but up-regulated by MLT. Of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) - induced mouse model with RORα levels reduced in the midbrain tissue, MLT treatment (intraperitoneal 20 mg/kg/d for 7 days) significantly increased the RORα levels and protected dopamine neurons, with decreased inflammation and increased anti-inflammatory M2-like phenotype in the microglia. Furthermore, siRNA-mediated knockdown implied the involvement of signal transducer and activator of transcription (STAT) pathway. In conclusion, MLT ameliorates neuroinflammation by inhibiting STAT-related pro-inflammatory (M1-like) polarization of microglia, revealing alternative options for neuroprotective treatment of PD.

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“…NF-κB is a redox-regulated transcription factors involving various responses such as pro-inflammation, inflammation, and oxidative stress (98). Typically, it is held in resting-state thought association with inhibitor of κB (IκB) proteins.…”

Section: Nuclear Factor κB Pathway and Inflammationmentioning

confidence: 99%

The Role of Oxidative Stress and Inflammation in X-Link Adrenoleukodystrophy

Chen

Guo

et al. 2022

Front. Nutr.

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X-linked adrenoleukodystrophy (X-ALD) is an inherited disease caused by a mutation in the ABCD1 gene encoding a peroxisomal transmembrane protein. It is characterized by the accumulation of very-long-chain fatty acids (VLCFAs) in body fluids and tissues, leading to progressive demyelination and adrenal insufficiency. ALD has various phenotypes, among which the most common and severe is childhood cerebral adrenoleukodystrophy (CCALD). The pathophysiological mechanisms of ALD remain unclear, but some in vitro/in vivo research showed that VLCFA could induce oxidative stress and inflammation, leading to damage. In addition, the evidence that oxidative stress and inflammation are increased in patients with X-ALD also proves that it is a potential mechanism of brain and adrenal damage. Therefore, normalizing the redox balance becomes a critical therapeutic target. This study focuses on the possible predictors of the severity and progression of X-ALD, the potential mechanisms of pathogenesis, and the promising targeted drugs involved in oxidative stress and inflammation.

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Role of melatonin in TLR4-mediated inflammatory pathway in the MTPT-induced mouse model

Cited by 15 publications

References 81 publications

Gut Microbiota: A Novel Therapeutic Target for Parkinson’s Disease

Gut Microbiota: A Novel Therapeutic Target for Parkinson’s Disease

Melatonin ameliorates Parkinson’s disease via regulating microglia polarization in a RORα‐dependent pathway

The Role of Oxidative Stress and Inflammation in X-Link Adrenoleukodystrophy

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