ArticleNeurotoxicity research2019
Caffeic Acid Phenethyl Ester (CAPE) Protects PC12 Cells Against Cisplatin-Induced Neurotoxicity by Activating the AMPK/SIRT1, MAPK/Erk, and PI3k/Akt Signaling Pathways.
Article in Neurotoxicity research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Protective potential of tween 80-functionalized chitosan-selenium nanoparticles containing quercetin against cisplatin neurotoxicity in PC12 cells: an in vitro and network pharmacology study.Scientific reports · 2025Article
- Molecular mechanisms underlying the neuroprotective effects of polyphenols: implications for cognitive function.EXCLI journal · 2025Review
- Caffeic acid phenethyl ester restores mitochondrial homeostasis against peritoneal fibrosis induced by peritoneal dialysis through the AMPK/SIRT1 pathway.Renal failure · 2024Article
- Plant phenolics inhibit focal adhesion kinase and suppress host cell invasion by uropathogenicInfection and immunity · 2024Article
- Caffeic acid phenethyl ester inhibits neuro-inflammation and oxidative stress following spinal cord injury by mitigating mitochondrial dysfunction via the SIRT1/PGC1α/DRP1 signaling pathway.Journal of translational medicine · 2024Article
- Sirtuins as Players in the Signal Transduction ofInternational journal of molecular sciences · 2024Review
- Baccharin from Brazilian green propolis induces neurotrophic signaling pathways in PC12 cells: potential for axonal and synaptic regeneration.Naunyn-Schmiedeberg's archives of pharmacology · 2022Article
- Piperine Provides Neuroprotection against Kainic Acid-Induced Neurotoxicity via Maintaining NGF Signalling Pathway.Molecules (Basel, Switzerland) · 2022Article
- Caffeic Acid Phenethyl Ester (CAPE) Improves Boar Sperm Quality and Antioxidant Capacity in Liquid Preservation (17°C) Linked to AMPK Activity Maintenance.Frontiers in veterinary science · 2022Article
- Protective Effect of Natural Antioxidants on Reducing Cisplatin-Induced Nephrotoxicity.Disease markers · 2022Review
- Recent progresses in the pharmacological activities of caffeic acid phenethyl ester.Naunyn-Schmiedeberg's archives of pharmacology · 2021Review
- CAPE and Neuroprotection: A Review.Biomolecules · 2021Review
- Neuroprotective Potential of Caffeic Acid Phenethyl Ester (CAPE) in CNS Disorders: Mechanistic and Therapeutic Insights.Current neuropharmacology · 2021Article
- The effect of alcoholic extract fromCell cycle (Georgetown, Tex.) · 2020Article
- Identification of Caffeic Acid Phenethyl Ester (CAPE) as a Potent Neurodifferentiating Natural Compound That Improves Cognitive and Physiological Functions in Animal Models of Neurodegenerative Diseases.Frontiers in aging neuroscience · 2020Article
- Natural Products and Their Bioactive Compounds: Neuroprotective Potentials against Neurodegenerative Diseases.Evidence-based complementary and alternative medicine : eCAM · 2020Review
- A Novel Schizophrenia Diagnostic Model Based on Statistically Significant Changes in Gene Methylation in Specific Brain Regions.BioMed research international · 2020Article
- MicroRNA‑217 inhibition relieves cerebral ischemia/reperfusion injury by targeting SIRT1.Molecular medicine reports · 2019Article
- FA-97, a New Synthetic Caffeic Acid Phenethyl Ester Derivative, Protects against Oxidative Stress-Mediated Neuronal Cell Apoptosis and Scopolamine-Induced Cognitive Impairment by Activating Nrf2/HO-1 Signaling.Oxidative medicine and cellular longevity · 2019Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Peripheral sensory neuropathy (PSN) is a well-known side effect of cisplatin characterized by axonal damage. In the early stage of neurotoxicity, cisplatin affects proteins that modulate neurite outgrowth and neuroplasticity, without inducing mitochondrial damage or apoptosis. There are no preventive therapies for cisplatin-induced peripheral neuropathy; therefore, measures to improve axonal growth and connectivity would be beneficial. Caffeic acid phenethyl ester (CAPE) is a bioactive component of propolis with neurotrophic and neuroprotective activities. We have recently showed that CAPE protects against cisplatin-induced neurotoxicity by activating NGF high-affinity receptors (trkA) and inducing neuroplasticity. We have now assessed other potential early targets of cisplatin and additional mechanisms involved in the neuroprotection of CAPE. Cisplatin reduced axonal cytoskeletal proteins (F-actin and β-III-tubulin) without inducing oxidative damage in PC12 cells. It also reduced energy-related proteins (AMPK α, p-AMPK α, and SIRT1) and glucose uptake. At this stage of neurotoxicity, glutamate excitotoxicity is not involved in the toxicity of cisplatin. CAPE attenuated the downregulation of the cytoskeleton and energy-related markers as well as SIRT1 and phosphorylated AMPK α. Moreover, the neuroprotective mechanism of CAPE also involves the activation of the neurotrophic signaling pathways MAPK/Erk and PI3k/Akt. The PI3K/Akt pathway is involved in the upregulation of SIRT1 induced by CAPE, but not in the upregulation of cytoskeletal proteins. Altogether, these findings suggest that the neuroprotective effect of CAPE against cisplatin-induced neurotoxicity involves both (a) a neurotrophic mechanism that mimics the mechanism triggered by the NGF itself and (b) a non-neurotrophic mechanism that upregulates the cytoskeletal proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.