The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
α-synuclein Induces Mitochondrial Dysfunction through Spectrin and the Actin Cytoskeleton
Open accessAbstract
Genetics and neuropathology strongly link α-synuclein aggregation and neurotoxicity to the pathogenesis of Parkinson's disease and related α-synucleinopathies. Here we describe a new Drosophila model of α-synucleinopathy based on widespread expression of wild-type human α-synuclein, which shows robust neurodegeneration, early-onset locomotor deficits, and abundant α-synuclein aggregation. We use results of forward genetic screening and genetic analysis in our new model to demonstrate that α-synuclein expression promotes reorganization of the actin filament network and consequent mitochondrial dysfunction through altered Drp1 localization. Similar changes are present in a mouse α-synucleinopathy model and in postmortem brain tissue from patients with α-synucleinopathy. Importantly, we provide evidence that the interaction of α-synuclein with spectrin initiates pathological alteration of the actin cytoskeleton and downstream neurotoxicity. These findings suggest new therapeutic approaches for α-synuclein induced neurodegeneration.
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
“Mitochondrial degeneration has been implicated in a-synucleinopathy (13,25) and a-syn transgenic flies show abnormal mitochondrial morphology (16).”
From Enhanced mTORC1 signaling and Protein Synthesis in Parkinson’s Disease Pathogenesis Disease Pathogenesis (2022) · cites this paper as [16]
The cited source says what the claim attributes to it.
In the citing paper
“The Drosophila Syb-QF2> a-syn model, which exhibits robust pathologic a-syn induced degeneration (16), showed a significant increase in P-S129 a-syn and d4EBP phosphorylation that was reduced by feeding the flies, the mTOR inhibitor, rapamycin (Figures 3C and3D).”
From Enhanced mTORC1 signaling and Protein Synthesis in Parkinson’s Disease Pathogenesis Disease Pathogenesis (2022) · cites this paper as [16]
In the citing paper
“and reinforced by recent studies on familial PD-linked genes such as,leucine-rich repeat kinase 2 (LRRK2), Parkin, synuclein alpha (SNCA), and DJ-1, as well as PD-like phenotypes resulting from genetic deletion of a catalytic ETC complex I subunit.184–187”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [187]
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
Staging of brain pathology related to sporadic Parkinson’s disease
Braak, H., Tredici, K. D., Rüb, U., de Vos, R. A. I., Jansen Steur, E. N. H., & Braak, E. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00065-9 · Cited by 10,777
Diagnosis and management of dementia with Lewy bodies: Third report of the DLB consortium
McKeith, I. G., Dickson, D. W., Lowe, J., Emre, M., O'Brien, J. T., Feldman, H., Cummings, J., Duda, J. E., Lippa, C., Perry, E. K., et al. (2005) · Neurology · doi:10.1212/01.wnl.0000187889.17253.b1 · Cited by 5,069
Mitochondrial Complex I Deficiency in Parkinson's Disease
Schapira, A. H. V., Cooper, J. M., Dexter, D., Clark, J. B., Jenner, P., & Marsden, C. D. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb02325.x · Cited by 2,283
α-Synuclein is phosphorylated in synucleinopathy lesions
Fujiwara, H., Hasegawa, M., Dohmae, N., Kawashima, A., Masliah, E., Goldberg, M. S., Shen, J., Takio, K., & Iwatsubo, T. (2002) · Nature Cell Biology · doi:10.1038/ncb748 · Cited by 2,174
A Drosophila model of Parkinson's disease
Feany, M. Β., & Bender, W. W. (2000) · Nature · doi:10.1038/35006074 · Cited by 2,156
Self-citationDynamin-related Protein Drp1 Is Required for Mitochondrial Division in Mammalian Cells
Smirnova, E., Griparić, L., Shurland, D., & van der Bliek, A. M. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.8.2245 · Cited by 1,938
α-Synuclein Promotes SNARE-Complex Assembly in Vivo and in Vitro
Burré, J., Sharma, M., Tsetsenis, T., Buchman, V. L., Etherton, M. R., & Südhof, T. C. (2010) · Science · doi:10.1126/science.1195227 · Cited by 1,907
Masliah, E., Rockenstein, E. M., Veinbergs, I., Mallory, M. E., Hashimoto, M., Takeda, A., Sagara, Y., Sisk, A., & Mucke, L. (2000) · Science · doi:10.1126/science.287.5456.1265 · Cited by 1,779
Alpha-synuclein and neurodegenerative diseases
Goedert, M. (2001) · Nature reviews. Neuroscience · doi:10.1038/35081564 · Cited by 1,428
Martínez‐Martín, P., Rodríguez‐Blázquez, C., Kurtis, M. M., Chaudhuri, К. R., & on Behalf of the NMSS Validation Group (2011) · Movement Disorders · doi:10.1002/mds.23462 · Cited by 1,043
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–227 of 227
Hou, X., Richardson, T., Heckman, M. G., Fiesel, F. C., White, L. J., Koga, S., Ross, O. A., Dickson, D. W., & Springer, W. (2025) · Acta Neuropathologica · doi:10.1007/s00401-025-02964-6 · Cited by 2
Perspectives for advancing neurotoxicity studies with Drosophila
Beamish, C. R., Dey, A., Sarkar, S., & Rand, M. D. (2023) · Advances in neurotoxicology · doi:10.1016/bs.ant.2023.03.004 · Cited by 1
Understanding Neurodegeneration and Neuroprotection Through Genetic Screens in Drosophila
Mandya, A. S., Cheramangalam, R. N., & Jaiswal, M. (2019) · Springer eBooks · doi:10.1007/978-981-13-2218-1_3 · Cited by 1
Belfiori-Carrasco, L. F., Rey, A. D., Ralbovszki, D. M., Jiménez-Ferrer, I., Bäckström, F., Balikai, S. S., Ahrén, D., Brolin, K. A., & Swanberg, M. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.03.22.533733 · Cited by 1
Khan, M. R., Yin, X., Kang, S.-U., Mitra, J., Wang, H., Brahmachari, S., Karuppagounder, S. S., Kimura, Y., Jhaldiyal, A., Kim, H. H., et al. (2022) · doi:10.1101/2022.10.03.510455
Mitochondria and Neurodegenerative Diseases
Johri, A., & Chandra, A. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.11474-6
Drosophila melanogaster: An Immaculate Model for Glial Research
Pragati, Tandon, S., Aqsa, A., Aggarwal, P., & Sarkar, S. (2022) · Springer eBooks · doi:10.1007/978-981-16-8313-8_26
Mitophagy Enhancer Identified in Repurposing Screen for Parkinson's Disease TherapeuticsPreprint
Moskal, N., Visanji, N. P., Gorbenko, O., Narasimhan, V., Nash, J., Lewis, P. N., & McQuibban, G. A. (2021) · SSRN Electronic Journal · doi:10.2139/ssrn.3904961
Moskal, N., Visanji, N. P., Gorbenko, O., Narasimhan, V., Tyrrell, H., Nash, J., Lewis, P. N., & McQuibban, G. A. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.05.18.492560
A Drosophila model of chemotherapy-related cognitive impairmentPreprint
Torre, M., Bukhari, H., Nithianandam, V., Zanella, C. A., Mata, D. A., & Feany, M. Β. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.06.01.543297
Self-citationSHH, nurr1, pitx3, and en1 models for Parkinson's disease
Ameen, G., Fahmy, H. M., Gaber, A., Abbas, F. M., & Soliman, R. I. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-16128-5.00007-4
Bouland, G. A., Tesi, N., Zhang, M., Ganz, A. B., Hulsman, M., van der Lee, S. J., Graat, M., Rozemüller, A. J. M., Huisman, M. A., van Schoor, N. M., et al. (2025) · medRxiv · doi:10.1101/2025.02.11.25322052
Urine Proteome Application in Neurodegenerative Diseases Biomarker Discovery
Wei, J., Zhao, M., Zhang, Y., & Li, L. (2025) · Springer eBooks · doi:10.1007/978-981-96-7886-0_14
Hsu, C.-H., Li, Y., Guo, T.-N., Tzou, F., Hong, C.-L., Lin, C., Huang, S., & Chan, C. (2025) · Autophagy · doi:10.1080/15548627.2025.2541384 · Cited by 1
Wafa, U. S., Begum, R. A., Alam, S., Jahan, H., Mamun, A. A., & Khandaker, A. M. (2025) · Biology Bulletin · doi:10.1134/s1062359024613417
Grebenik, E. A., Zaichick, S., Gomez, A., & Caraveo, G. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.05.674494
Yue, X., Dulac, A., Hu, A., Rahmani, Z., & Birman, S. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.03.673979
Sarkar, S., Bardai, F. H., Olsen, A. L., Lohr, K. M., Zhang, Y.-Y., & Feany, M. Β. (2021) · Figshare · doi:10.6084/m9.figshare.14670513
Self-citationGarzillo, K., Perulli, M., & Babcock, D. T. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.17.699798
Kim, S. Y., Choi, J., Jang, D. C., Lee, P. R., Hong, G., Kim, J., Jeong, W., Han, K., & Kwon, S. (2026) · npj Parkinson s Disease · doi:10.1038/s41531-026-01277-z · Cited by 1
Reina-Gonzalez, P., Cesur, M. F., Anchan, A., Abu-Salah, A., Çakır, T., Malovic, E., & Sarkar, S. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.02.703282
Pragati, Congdon, E. E., Jiang, Y., Erdjument‐Bromage, H., Huang, H.-W., Pan, R., Marchal, I. S., Kong, X., Neubert, T. A., Ryoo, H. D., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.07.735601
Averbukh, M., Wang, T., Garcia, G., & Higuchi‐Sanabria, R. (2026) · Journal of Cell Science · doi:10.1242/jcs.264775
Genetics of α-Synuclein: The Prime Pathological Player of Parkinson’s Disease
Sarhadi, T. R., Joshi, N., Raveendran, A., Panse, J. S., & Nagotu, S. (2026) · Neurotoxicity Research · doi:10.1007/s12640-026-00827-w
Metadata
- Authors
- Ordonez, D. G., Lee, M. K., & Feany, M. B.
- Affiliations
- Brigham and Women's Hospital (US)
- University of Minnesota (US)
- ORCID
- Lee, Michael K.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 97
- Issue
- 1
- Pages
- 108-124.e6
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC5755717
- OpenAlex
- W2771082365
- Cited by
- 227
- References
- 66
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 31 · 2023: 24 · 2022: 30 · 2021: 41 · 2020: 31 · 2019: 26 · 2018: 13
- FWCI
- 13.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Science Foundation (DGE1745303, DGE1144152)
- National Institutes of Health (R01-NS086074, R01-NS092093, R01-AG044113, R01-NS083391)
- 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
- alpha-synuclein, Parkinson's disease, synucleinopathies, spectrin, actin cytoskeleton, mitochondrial dysfunction, Drp1, mitochondrial fission, Drosophila model, neurodegeneration, alpha-synuclein aggregation, locomotor deficits, forward genetic screen
- MeSH terms
- Aged, Aged, 80 and over, Animals, Cytoskeletal Proteins, Disease Models, Animal, Drosophila melanogaster, Female, Humans, Male, Actin Cytoskeleton, Middle Aged, Mitochondria, Nerve Degeneration, Spectrin, GTP-Binding Proteins, Lewy Body Disease, alpha-Synuclein
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
