ArticleBioMed research international2013
Rotenone upregulates alpha-synuclein and myocyte enhancer factor 2D independently from lysosomal degradation inhibition.
Article in BioMed research international, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
- Innovative approach in Parkinson's targeting via berberine-loaded mucoadhesive surface-modified liposomes: a multi-faceted study.BMC pharmacology & toxicology · 2025Article
- Soil to Synapse: Molecular Insights into the Neurotoxicity of Common Gardening Chemicals in Alzheimer's and Parkinson's Disease.International journal of molecular sciences · 2025Review
- Chronic DSS-Induced Colitis Exacerbates Parkinson's Disease Phenotype and Its Pathological Features Following Intragastric Rotenone Exposure.ACS pharmacology & translational science · 2025Article
- Empagliflozin repurposing in Parkinson's disease; modulation of oxidative stress, neuroinflammation, AMPK/SIRT-1/PGC-1α, and wnt/β-catenin pathways.Inflammopharmacology · 2024Article
- The Molecular and Biological Function of MEF2D in Leukemia.Advances in experimental medicine and biology · 2024Review
- Neuroprotective Effect of Swertiamarin in a Rotenone Model of Parkinson's Disease: Role of Neuroinflammation and Alpha-Synuclein Accumulation.ACS pharmacology & translational science · 2023Article
- Neuroprotective Effect of Phloretin in Rotenone-Induced Mice Model of Parkinson's Disease: Modulating mTOR-NRF2-p62 Mediated Autophagy-Oxidative Stress Crosstalk.Journal of Alzheimer's disease : JAD · 2023Article
- Intranasal Exposure to Low-Dose Rotenone Induced Alpha-Synuclein Accumulation and Parkinson's Like Symptoms Without Loss of Dopaminergic Neurons.Neurotoxicity research · 2022Article
- Contribution of Autophagy-Lysosomal Pathway in the Exosomal Secretion of Alpha-Synuclein and Its Impact in the Progression of Parkinson's Disease.Frontiers in molecular neuroscience · 2022Review
- Biogenic zinc-oxide nanoparticles ofBiochemistry and biophysics reports · 2021Article
- Vulnerability of subcellular structures to pathogenesis induced by rotenone in SH-SY5Y cells.Physiological research · 2021Article
- Direct current stimulation enhances neuronal alpha-synuclein degradation in vitro.Scientific reports · 2021Article
- Ndfip1 Prevents Rotenone-Induced Neurotoxicity and Upregulation of α-Synuclein in SH-SY5Y Cells.Frontiers in molecular neuroscience · 2020Article
- Article
- Lycopodium Attenuates Loss of Dopaminergic Neurons by Suppressing Oxidative Stress and Neuroinflammation in a Rat Model of Parkinson's Disease.Molecules (Basel, Switzerland) · 2019Article
- MEF-2 isoforms' (A-D) roles in development and tumorigenesis.Oncotarget · 2019Review
- Malfunctioning of Chaperone-Mediated Autophagy in Parkinson's Disease: Feats, Constraints, and Flaws of Modulators.Neurotoxicity research · 2019Review
- MEF2D Mediates the Neuroprotective Effect of Methylene Blue Against Glutamate-Induced Oxidative Damage in HT22 Hippocampal Cells.Molecular neurobiology · 2017Article
- CSF Nrf2 and HSPA8 in Parkinson's disease patients with and without LRRK2 gene mutations.Journal of neural transmission (Vienna, Austria : 1996) · 2016Article
- Role of Chaperone-Mediated Autophagy Dysfunctions in the Pathogenesis of Parkinson's Disease.Frontiers in molecular neuroscience · 2016Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysfunctions of chaperone-mediated autophagy (CMA), the main catabolic pathway for alpha-synuclein, have been linked to the pathogenesis of Parkinson's disease (PD). Since till now there is limited information on how PD-related toxins may affect CMA, in this study we explored the effect of mitochondrial complex I inhibitor rotenone on CMA substrates, alpha-synuclein and MEF2D, and effectors, lamp2A and hsc70, in a human dopaminergic neuroblastoma SH-SY5Y cell line. Rotenone induced an upregulation of alpha-synuclein and MEF2D protein levels through the stimulation of their de novo synthesis rather than through a reduction of their CMA-mediated degradation. Moreover, increased MEF2D transcription resulted in higher nuclear protein levels that exert a protective role against mitochondrial dysfunction and oxidative stress. These results were compared with those obtained after lysosome inhibition with ammonium chloride. As expected, this toxin induced the cytosolic accumulation of both alpha-synuclein and MEF2D proteins, as the result of the inhibition of their lysosome-mediated degradation, while, differently from rotenone, ammonium chloride decreased MEF2D nuclear levels through the downregulation of its transcription, thus reducing its protective function. These results highlight that rotenone affects alpha-synuclein and MEF2D protein levels through a mechanism independent from lysosomal degradation inhibition.
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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.