The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
Isogenic Human iPSC Parkinson’s Model Shows Nitrosative Stress-Induced Dysfunction in MEF2-PGC1α Transcription
Open accessAbstract
SUMMARY Parkinson’s disease (PD) is characterized by loss of A9 dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). An association has been reported between PD and exposure to mitochondrial toxins, including environmental pesticides paraquat, maneb, and rotenone. Here, using a robust, patient-derived stem cell model of PD allowing comparison of A53T α-synuclein (α-syn) mutant cells and isogenic mutation-corrected controls, we identify mitochondrial toxin-induced perturbations in A53T α-syn A9 DA neurons (hNs). We report a pathway whereby basal and toxin-induced nitrosative/oxidative stress results in S-nitrosylation of transcription factor MEF2C in A53T hNs compared to corrected controls. This redox reaction inhibits the MEF2C-PGC1α transcriptional network, contributing to mitochondrial dysfunction and apoptotic cell death. Our data provide mechanistic insight into gene-environmental interaction (GxE) in the pathogenesis of PD. Furthermore, using small-molecule high-throughput screening, we identify the MEF2C-PGC1α pathway as a therapeutic target to combat PD.
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Metadata
- Authors
- Ryan, S. D., Dolatabadi, N., Chan, S. F., Zhang, X., Akhtar, M. W., Parker, J., Soldner, F., Sunico, C. R., Nagar, S., Talantova, M., Lee, B., Lopez, K., Nutter, A., Shan, B., Molokanova, E., Zhang, Y., Han, X., Nakamura, T., Masliah, E., Yates, J. R., Nakanishi, N., Andreyev, A. Y., Okamoto, S.-I., Jaenisch, R., Ambasudhan, R., & Lipton, S. A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 155
- Issue
- 6
- Pages
- 1351-1364
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2130916594
- Cited by
- 434
- References
- 60
- FWCI
- 21.28
- Type
- journal article
- Language
- en
- Update notices
- erratum (2013-12-19)
- Open access
- bronze
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 369 d)
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- Ryan, S. D., Dolatabadi, N., Chan, S. F., Zhang, X., Akhtar, M. W., Parker, J., Soldner, F., Sunico, C. R., Nagar, S., Talantova, M., Lee, B., Lopez, K., Nutter, A., Shan, B., Molokanova, E., Zhang, Y., Han, X., Nakamura, T., Masliah, E., . . . Lipton, S. A. (2013). Isogenic Human iPSC Parkinson’s Model Shows Nitrosative Stress-Induced Dysfunction in MEF2-PGC1α Transcription. Cell. https://doi.org/10.1016/j.cell.2013.11.009
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
