ArticlePloS one2013
The Fas/Fas ligand death receptor pathway contributes to phenylalanine-induced apoptosis in cortical neurons.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 32 citations in OpenAlex.
- Label-Free SERS Analysis of Glioma Cells to Detect Drug Resistance Using Metabolic Phenylalanine Level.ACS measurement science au · 2026Article
- Endoplasmic reticulum stress pathways and cellular death mechanisms in patients with phenylketonuria.Molecular biology reports · 2025Article
- Genetically predicted amino acids related to neural regulation mediate the association between diabetes mellitus and postherpetic neuralgia: a Mendelian randomization study.Diabetology & metabolic syndrome · 2025Article
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- Insights from Animal Models on the Pathophysiology of Hyperphenylalaninemia: Role of Mitochondrial Dysfunction, Oxidative Stress and Inflammation.Molecular neurobiology · 2021Review
- Synergistic anticancer effect of docosahexaenoic acid and isoliquiritigenin on human colorectal cancer cells through ROS-mediated regulation of the JNK and cytochrome c release.Molecular biology reports · 2021Article
- 6,7-Dihydroxy-2-(4'-hydroxyphenyl)naphthalene induces HCT116 cell apoptosis through activation of endoplasmic reticulum stress and the extrinsic apoptotic pathway.Drug design, development and therapy · 2019Article
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- Control of Mitochondrial Dynamics by Fas-induced Caspase-8 Activation in Hippocampal Neurons.Experimental neurobiology · 2015Article
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- Huachansu suppresses human bladder cancer cell growth through the Fas/Fasl and TNF- alpha/TNFR1 pathway in vitro and in vivo.Journal of experimental & clinical cancer research : CR · 2015Article
- IgLON cell adhesion molecules are shed from the cell surface of cortical neurons to promote neuronal growth.The Journal of biological chemistry · 2015Article
- Isoflurane Damages the Developing Brain of Mice and Induces Subsequent Learning and Memory Deficits through FASL-FAS Signaling.BioMed research international · 2015Article
- NF-κB regulates caspase-4 expression and sensitizes neuroblastoma cells to Fas-induced apoptosis.PloS one · 2015Article
- Implications of biomarkers in human hepatocellular carcinoma pathogenesis and therapy.World journal of gastroenterology · 2014Review
- Time-Dependent Regulation of Apoptosis by AEN and BAX in Response to 2-Aminoanthracene Dietary Consumption.Toxicology international · 2014Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phenylketonuria (PKU), an autosomal recessive disorder of amino acid metabolism caused by mutations in the phenylalanine hydroxylase (PAH) gene, leads to childhood mental retardation by exposing neurons to cytotoxic levels of phenylalanine (Phe). A recent study showed that the mitochondria-mediated (intrinsic) apoptotic pathway is involved in Phe-induced apoptosis in cultured cortical neurons, but it is not known if the death receptor (extrinsic) apoptotic pathway and endoplasmic reticulum (ER) stress-associated apoptosis also contribute to neurodegeneration in PKU. To answer this question, we used specific inhibitors to block each apoptotic pathway in cortical neurons under neurotoxic levels of Phe. The caspase-8 inhibitor Z-IETD-FMK strongly attenuated apoptosis in Phe-treated neurons (0.9 mM, 18 h), suggesting involvement of the Fas receptor (FasR)-mediated cell death receptor pathway in Phe toxicity. In addition, Phe significantly increased cell surface Fas expression and formation of the Fas/FasL complex. Blocking Fas/FasL signaling using an anti-Fas antibody markedly inhibited apoptosis caused by Phe. In contrast, blocking the ER stress-induced cell death pathway with salubrinal had no effect on apoptosis in Phe-treated cortical neurons. These experiments demonstrate that the Fas death receptor pathway contributes to Phe-induced apoptosis and suggest that inhibition of the death receptor pathway may be a novel target for neuroprotection in PKU patients.
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