The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Rotenone selectively kills serotonergic neurons through a microtubule‐dependent mechanism
Open accessAbstract
As a major co‐morbidity of Parkinson’s disease (PD), depression is associated with the loss of serotonergic neurons. Our recent study has shown that midbrain dopaminergic neurons are particularly vulnerable to microtubule‐depolymerizing agents including rotenone, an environmental toxin linked to PD. Here we show that rotenone also selectively killed serotonergic neurons in midbrain neuronal cultures. Its selective toxicity was significantly decreased by the microtubule‐stabilizing drug taxol and mimicked by microtubule‐depolymerizing agents such as colchicine and nocodazole. Microtubule depolymerization induced by rotenone or colchicine caused vesicle accumulation in the soma and killed serotonergic neurons through a mechanism dependent on serotonin metabolism in the cytosol. Blocking serotonin synthesis or degradation, as well as application of antioxidants, significantly reduced the selective toxicity of rotenone or colchicine. Inhibition of vesicular sequestration of serotonin exerted a selective toxicity on serotonergic neurons that was mitigated by blocking serotonin metabolism. Over‐expression of parkin, a protein‐ubiquitin E3 ligase that strongly binds to microtubules, greatly attenuated the selective toxicity of rotenone or colchicine. The protective effects of parkin were abrogated by its PD‐linked mutations. Together, our results suggest that rotenone and parkin affect the survival of serotonergic neurons by impacting on microtubules in opposing manners.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“For example, the CI inhibitor rotenone destabilizes microtubules, 40,41 and the CII inhibitor α-TOS as well as the complex III inhibitor antimycin act as BH3 mimetics.42,43”
From Ubiquinone-binding site mutagenesis reveals the role of mitochondrial complex II in cell death initiation (2015) · cites this paper as [41]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Microtubules as a target for anticancer drugs
Jordan, M. A., & Wilson, L. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1317 · Cited by 4,000
Chronic systemic pesticide exposure reproduces features of Parkinson's disease
Betarbet, R. S., Sherer, T., MacKenzie, G. M., Garcia‐Osuna, M., Panov, A. V., & Greenamyre, J. T. (2000) · Nature Neuroscience · doi:10.1038/81834 · Cited by 3,770
The Neuropathologic Basis of Different Clinical Subgroups of Parkinson's Disease
Paulus, W., & Jellinger, K. A. (1991) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199111000-00006 · Cited by 556
Inhibition of Electron and Energy Transfer in Mitochondria
Chance, B., & Hollunger, G. (1963) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)84014-0 · Cited by 366
Prevalence, etiology, and treatment of depression in Parkinson’s disease
McDonald, W. M., Richard, I. H., & DeLong, M. R. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00530-4 · Cited by 358
Altered serotonin metabolism in depressed patients with Parkinson's disease
Mayeux, R. P., Stern, Y., COTE, L. J., & Williams, J. B. W. (1984) · Neurology · doi:10.1212/wnl.34.5.642 · Cited by 343
Parkin Binds to α/β Tubulin and Increases their Ubiquitination and Degradation
Ren, Y., Zhao, J., & Feng, J. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-08-03316.2003 · Cited by 317
Self-citationTHE ROLE OF VESICULAR TRANSPORT PROTEINS IN SYNAPTIC TRANSMISSION AND NEURAL DEGENERATION
Liu, Y., & Edwards, R. H. (1997) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.20.1.125 · Cited by 295
Parkin binds to alpha/beta tubulin and increases their ubiquitination and degradation.
Ren, Y., Zhao, J., & Feng, J. (2003) · PubMed · Cited by 285
Self-citationAn Estimate of the Incidence of Depression in Idiopathic Parkinson's Disease
Dooneief, G., Mirabello, E., Bell, K., Marder, K. S., Stern, Y., & Mayeux, R. P. (1992) · Archives of Neurology · doi:10.1001/archneur.1992.00530270125028 · Cited by 211
Cited by
Sorted by citations
Kluckova, K., Sticha, M., Cerny, J., Mracek, T., Dong, L., Drahota, Z., Gottlieb, E., Neuzil, J., & Rohlena, J. (2015) · Cell Death & Disease · doi:10.1038/cddis.2015.110 · Cited by 66
Metadata
- Authors
- Ren, Y., & Feng, J.
- Affiliations
- University at Buffalo, State University of New York (US)
- Corresponding author
- Feng, Jian
- ORCID
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2007-06-03
- Volume
- 103
- Issue
- 1
- Pages
- 303-311
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2094552119
- Cited by
- 65
- References
- 30
- Citations by year
- 2026: 3 · 2025: 2 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 7 · 2012: 2
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS4172)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- rotenone, serotonergic neurons, microtubule depolymerization, Parkinson's disease, depression, Parkin, colchicine, nocodazole, serotonin metabolism, neurotoxicity, midbrain neurons
- MeSH terms
- Amobarbital, Animals, Cells, Cultured, Colchicine, Mesencephalon, Microtubules, Neurons, Parkinson Disease, Rotenone, Serotonin, Cell Death, Electron Transport Complex I, Ubiquitin-Protein Ligases, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
