Tryptophan in the diet ameliorates motor deficits in a rotenone‐induced rat Parkinson's disease model via activating the aromatic hydrocarbon receptor pathway

Wang, Yilin; Chen, Shuangxi; Tan, Jian; Gao, Yijiang; Yan, Hongye; Liu, Yao; Yi, Shanqing; Xiao, Zijian; Wu, Honglu

doi:10.1002/brb3.2226

Cited by 16 publications

(11 citation statements)

References 46 publications

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“…Locomotor dysfunction serves as a wide-acknowledged clinical symptom of PD [23]. In our previous study, we observed that dietary tryptophan can ameliorate the impaired motor function in PD [47], in the current study, we revealed that MA-5 can promote the recovery of the motor function in mice induced by MPTP via activating the AMPK-mediated autophagy.…”

supporting

confidence: 60%

Mitochonic acid 5 ameliorates the motor deficits in the MPTP-induced mouse Parkinson’s disease model by AMPK-mediated autophagy

Wan¹,

Gao²,

Tan³

et al. 2022

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Parkinson's disease (PD) is a well-known neurodegenerative disorder characterized by the degeneration of dopaminergic neurons, and oxidative stress and neuroinflammation are also associated with the pathogenesis of PD. Mitochonic acid 5 , an analogue of indole-3-acetic acid, exerts key protective roles in inhibiting apoptosis, oxidative stress and neuroinflammation in multiple diseases. However, whether MA-5 can be beneficial for PD remains unclear. Hence, the aim of this study was to investigate the neuroprotective role of MA-5 in PD. In the current study, MPTP-challenged mice were treated as the in vivo model, and the effect of MA-5 on the motor function, neuronal survival, oxidative stress, neuroinflammation and the underlying mechanisms involved with AMPK and autophagy were determined. We revealed that MA-5 obviously up-regulated the phosphorylation of AMPK and promoted the autophagy (indicated by the increased LC3II/LC3I, parkin, pink and decreased p62) in substantia nigra (SN), ameliorated the motor deficits, up-regulated the expression of TH, suppressed the inflammation (indicated by the decreased protein levels of interleukin (IL)-1β, IL-6, tumour necrosis factor α) in SN in MPTP-induced mice. However, these patterns were reversed after the treatment of Compound C, an inhibitor of AMPK; also, after the application of CSA, an inhibitor of autophagy, MA-5 cannot play against the neurotoxicity of MPTP in mice. These combined results suggest that MA-5 can protect against MPTP-induced neurotoxicity to ameliorate the impaired motor function, which may be modulated via activation of AMPK-induced autophagy.

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supporting

confidence: 60%

Mitochonic acid 5 ameliorates the motor deficits in the MPTP-induced mouse Parkinson’s disease model by AMPK-mediated autophagy

Wan¹,

Gao²,

Tan³

et al. 2022

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“…Chronic exposure to both chemicals has been linked to the development of Parkinson’s disease (PD) in mice, rats and humans ( 14 ). In a manner similar to haloperidol, dietary tryptophan improves the impaired motor functions in rotenone-induced rat models of PD ( 15 ). The benefits of tryptophan in animals exposed to haloperidol, rotenone and paraquat, along with the sensitivity of yeast trp Δ/ aro Δ mutants to all 3 compounds (Fig.…”

Section: Resultsmentioning

confidence: 99%

Global analysis of the yeast knock-out phenome

Turco

Chang

Wang

et al. 2022

Preprint

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Genome-wide phenotypic screens in the budding yeast Saccharomyces cerevisiae have produced the largest, richest and most systematic phenotypic description of any organism. Such an achievement was enabled by the development of highly scalable phenotypic assays and construction of the yeast knock-out (YKO) collection, comprising ~5,000 isogenic strains each deleted for exactly one open reading frame. Systematic screening of the YKO collection led to ~500 publications describing ~14,500 phenotypes capturing nearly every aspect of yeast biology. Yet, integrative analyses of this rich data source have been virtually impossible due to the lack of a central repository and consistent meta-data annotations. Here, we describe the aggregation, harmonization and analysis of all published phenotypic screens of the YKO collection, which we refer to as the Yeast Phenome (www.yeastphenome.org). To demonstrate the power of data integration and illustrate how much it facilitates the generation of testable hypotheses, we present three discoveries uniquely enabled by Yeast Phenome. First, we use the variation in the number of phenotypes per gene to identify tryptophan homeostasis as a central point of vulnerability to a wide range of chemical compounds, including FDA-approved drugs. Second, using phenotypic profiles as a tool for predicting gene function, we identify and validate the role of YHR045W as a novel regulator of ergosterol biosynthesis and DNA damage response, and YGL117W as a new member of the aromatic amino acid biosynthesis pathway. Finally, we describe a surprising exponential relationship between phenotypic similarity and intergenic distance in both yeast and human genomes. This relationship, which stretches as far as 380 kb in yeast and 100 Mb in humans, suggests that gene positions are optimized for function to a much greater extent than appreciated previously. Overall, we show that Yeast Phenome enables systematic enquiries into the nature of gene-gene and gene-phenotype relationships and is an important new resource for systems biology.

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“…The aryl hydrocarbon receptor (AhR), often referred to as the dioxin receptor, is a ligand-activated transcription factor that is widely expressed centrally and systemically. AHR signaling is thought to be an important component of the barrier site immune response and can regulate a variety of cellular processes, including immune regulation, cell development, differentiation, proliferation, survival, and apoptosis ( 110 , 111 ). AhR forms a protein complex with dimer of the 90 kDa heat shock protein (HSP90), AhR-interacting protein (AIP), the co-chaperone p23, and the protein kinase SRC, which is expressed in the cytoplasm ( 112 ).…”

Section: Regulation Of Trp Metabolism On Downstream Targetsmentioning

confidence: 99%

“…The collection of urine samples is also simpler than that of blood or cerebrospinal fluid, making urine detection a non-invasive and accessible method. Yilin Wang ( 111 ) found that TRP supplementation inhibited nuclear translocation of NF-κB in a PD model. However, With the use of AhR pathway inhibitors, TRP’s neuroprotective effects and its suppression of NF-κB were reversed.…”

Section: Trp Metabolism In Neurological and Psychiatric Disordersmentioning

confidence: 99%

Tryptophan metabolism: Mechanism-oriented therapy for neurological and psychiatric disorders

Long

et al. 2022

Front. Immunol.

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Neurological and psychiatric disorders are a category of chronic diseases that are widespread and pose serious mental and physical health problems for patients. The substrates, products, and enzymes of Tryptophan metabolism all contribute to the development of neurological and psychiatric disorders. This paper deals with three metabolic pathways of tryptophan that produce a series of metabolites called tryptophan Catabolics (TRYCATs). These metabolites are involved in pathological processes such as excitotoxicity, neuroinflammation, oxidative stress, and mitochondrial damage and are closely associated with neurological and psychiatric disorders such as Alzheimer’s disease and depression. Here, we review the elements that affect how tryptophan metabolism is regulated, including inflammation and stress, exercise, vitamins, minerals, diet and gut microbes, glucocorticoids, and aging, as well as the downstream regulatory effects of tryptophan metabolism, including the regulation of glutamate (Glu), immunity, G-protein coupled receptor 35 (Gpr35), nicotinic acetylcholine receptor (nAChR), aryl hydrocarbon receptor (AhR), and dopamine (DA). In order to advance the general understanding of tryptophan metabolism in neurological and psychiatric disorders, this paper also summarizes the current situation and effective drugs of tryptophan metabolism in the treatment of neurological and psychiatric disorders and considers its future research prospects.

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Tryptophan in the diet ameliorates motor deficits in a rotenone‐induced rat Parkinson's disease model via activating the aromatic hydrocarbon receptor pathway

Cited by 16 publications

References 46 publications

Mitochonic acid 5 ameliorates the motor deficits in the MPTP-induced mouse Parkinson’s disease model by AMPK-mediated autophagy

Mitochonic acid 5 ameliorates the motor deficits in the MPTP-induced mouse Parkinson’s disease model by AMPK-mediated autophagy

Global analysis of the yeast knock-out phenome

Tryptophan metabolism: Mechanism-oriented therapy for neurological and psychiatric disorders

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