β‐Methylphenylalanine exerts neuroprotective effects in a Parkinson's disease model by protecting against tyrosine hydroxylase depletion

Yao, Feng; Ma, Jianjun; Yuan, Lipin

doi:10.1111/jcmm.15571

Cited by 8 publications

(2 citation statements)

References 26 publications

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“…Past research found that octanoylcarnitine and decanoylcarnitine were closely correlated with the treatment effect of ESCC (26). (2S,3S)-3-Methylphenylalanine can prevent mitochondrial damage and reduce apoptosis of cells (40). The level of 3-(pyrazol-1-yl)-L-alanine is closely related to gastric cancers (41).…”

Section: Discussionmentioning

confidence: 96%

Serum Metabolomic Profiling Reveals Biomarkers for Early Detection and Prognosis of Esophageal Squamous Cell Carcinoma

et al. 2022

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Esophageal squamous cell carcinoma (ESCC) is one of the most common aggressive malignancies worldwide, particularly in northern China. The absence of specific early symptoms and biomarkers leads to late-stage diagnosis, while early diagnosis and risk stratification are crucial for improving overall prognosis. We performed UPLC-MS/MS on 450 ESCC patients and 588 controls consisting of a discovery group and two validation groups to identify biomarkers for early detection and prognosis. Bioinformatics and clinical statistical methods were used for profiling metabolites and evaluating potential biomarkers. A total of 105 differential metabolites were identified as reliable biomarker candidates for ESCC with the same tendency in three cohorts, mainly including amino acids and fatty acyls. A predictive model of 15 metabolites [all-trans-13,14-dihydroretinol, (±)-myristylcarnitine, (2S,3S)-3-methylphenylalanine, 3-(pyrazol-1-yl)-L-alanine, carnitine C10:1, carnitine C10:1 isomer1, carnitine C14-OH, carnitine C16:2-OH, carnitine C9:1, formononetin, hyodeoxycholic acid, indole-3-carboxylic acid, PysoPE 20:3, PysoPE 20:3(2n isomer1), and resolvin E1] was developed by logistic regression after LASSO and random forest analysis. This model held high predictive accuracies on distinguishing ESCC from controls in the discovery and validation groups (accuracies > 89%). In addition, the levels of four downregulated metabolites [hyodeoxycholic acid, (2S,3S)-3-methylphenylalanine, carnitine C9:1, and indole-3-carboxylic acid] were significantly higher in early cancer than advanced cancer. Furthermore, three independent prognostic markers were identified by multivariate Cox regression analyses with and without clinical indicators: a high level of MG(20:4)isomer and low levels of 9,12-octadecadienoic acid and L-isoleucine correlated with an unfavorable prognosis; the risk score based on these three metabolites was able to stratify patients into low or high risk. Moreover, pathway analysis indicated that retinol metabolism and linoleic acid metabolism were prominent perturbed pathways in ESCC. In conclusion, metabolic profiling revealed that perturbed amino acids and lipid metabolism were crucial metabolic signatures of ESCC. Both panels of diagnostic and prognostic markers showed excellent predictive performances. Targeting retinol and linoleic acid metabolism pathways may be new promising mechanism-based therapeutic approaches. Thus, this study would provide novel insights for the early detection and risk stratification for the clinical management of ESCC and potentially improve the outcomes of ESCC.

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Section: Discussionmentioning

confidence: 96%

Serum Metabolomic Profiling Reveals Biomarkers for Early Detection and Prognosis of Esophageal Squamous Cell Carcinoma

et al. 2022

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“…In the retina, dopamine is synthesized by subtype A18 cells without long protrusions or cells of the inner plexiform layer (Lin 2011), which are mainly found in the inner plexiform and inner nuclear layers of the retina (Jackson, et al 2014) and can affect the activity of a variety of cells within the retina (Lin 2011). TH is the rate-limiting enzyme for dopamine synthesis, and its level is indicative of dopamine levels (Feng, et al 2020). This study found that the TH uorescence intensity in the inner plexiform and inner nuclear layers of the left retina (contralateral to the lesion) was reduced by more than 80% and 90%, respectively, in the PD group compared with the control group at 14 and 28 days after lesioning and that the TH uorescence intensity in bilateral retina increased signi cantly after magnesium sulfate supplementation, suggesting that the loss of retinal dopaminergic neurons in PD rats increased with the progression of PD.…”

Section: Discussionmentioning

confidence: 99%

Magnesium sulfate protects retinal dopaminergic neurons in rats with 6-OHDA-induced Parkinson’s disease

Huang,

Lin,

Zhang

et al. 2023

Preprint

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Parkinson's disease (PD) is one of the most common neurodegenerative diseases. The main pathological features of PD are the degeneration and death of dopamine neurons in the substantia nigra-striatal pathway and the accumulation of Lewy bodies in neurons. In addition to the well-known hallmark symptoms such as resting tremor and muscle rigidity, Parkinson's patients also experience non-motor symptoms such as visual disturbances, hyposmia, and sleep disturbances. At the same time, visual disturbances appear earlier than motor symptoms. The visual dysfunction in early-stage of Parkinson's disease indicates the occurrence and development of the disease. The visual dysfunction in Parkinson's disease is due to the damage of retinal dopamine neurons. This study found that magnesium sulfate supplementation can effectively delay the death of retinal dopamine neurons in 6-OHDA induced rat model of PD and improve the motor symptoms of rats with anxiety-like behavior. Therefore, magnesium sulfate may provide a new option for the early diagnosis and treatment of Parkinson's disease.

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Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors

et al. 2021

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Inhibition of complex I of the mitochondrial respiratory chain (cI) by rotenone and methyl-phenylpyridinium (MPP +) leads to the degeneration of dopaminergic neurons in man and rodents. To formally describe this mechanism of toxicity, an adverse outcome pathway (AOP:3) has been developed that implies that any inhibitor of cI, or possibly of other parts of the respiratory chain, would have the potential to trigger parkinsonian motor deficits. We used here 21 pesticides, all of which are described in the literature as mitochondrial inhibitors, to study the general applicability of AOP:3 or of in vitro assays that are assessing its activation. Five cI, three complex II (cII), and five complex III (cIII) inhibitors were characterized in detail in human dopaminergic neuronal cell cultures. The NeuriTox assay, examining neurite damage in LUHMES cells, was used as in vitro proxy of the adverse outcome (AO), i.e., of dopaminergic neurodegeneration. This test provided data on whether test compounds were unspecific cytotoxicants or specifically neurotoxic, and it yielded potency data with respect to neurite degeneration. The pesticide panel was also examined in assays for the sequential key events (KE) leading to the AO, i.e., mitochondrial respiratory chain inhibition, mitochondrial dysfunction, and disturbed proteostasis. Data from KE assays were compared to the NeuriTox data (AO). The cII-inhibitory pesticides tested here did not appear to trigger the AOP:3 at all. Some of the cI/cIII inhibitors showed a consistent AOP activation response in all assays, while others did not. In general, there was a clear hierarchy of assay sensitivity: changes of gene expression (biomarker of neuronal stress) correlated well with NeuriTox data; mitochondrial failure (measured both by a mitochondrial membrane potential-sensitive dye and a respirometric assay) was about 10–260 times more sensitive than neurite damage (AO); cI/cIII activity was sometimes affected at > 1000 times lower concentrations than the neurites. These data suggest that the use of AOP:3 for hazard assessment has a number of caveats: (i) specific parkinsonian neurodegeneration cannot be easily predicted from assays of mitochondrial dysfunction; (ii) deriving a point-of-departure for risk assessment from early KE assays may overestimate toxicant potency.

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β‐Methylphenylalanine exerts neuroprotective effects in a Parkinson's disease model by protecting against tyrosine hydroxylase depletion

Cited by 8 publications

References 26 publications

Serum Metabolomic Profiling Reveals Biomarkers for Early Detection and Prognosis of Esophageal Squamous Cell Carcinoma

Serum Metabolomic Profiling Reveals Biomarkers for Early Detection and Prognosis of Esophageal Squamous Cell Carcinoma

Magnesium sulfate protects retinal dopaminergic neurons in rats with 6-OHDA-induced Parkinson’s disease

Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors

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