The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
ER Stress and Autophagic Perturbations Lead to Elevated Extracellular α-Synuclein in GBA-N370S Parkinson's iPSC-Derived Dopamine Neurons
Open accessAbstract
Heterozygous mutations in the glucocerebrosidase gene (GBA) represent the strongest common genetic risk factor for Parkinson's disease (PD), the second most common neurodegenerative disorder. However, the molecular mechanisms underlying this association are still poorly understood. Here, we have analyzed ten independent induced pluripotent stem cell (iPSC) lines from three controls and three unrelated PD patients heterozygous for the GBA-N370S mutation, and identified relevant disease mechanisms. After differentiation into dopaminergic neurons, we observed misprocessing of mutant glucocerebrosidase protein in the ER, associated with activation of ER stress and abnormal cellular lipid profiles. Furthermore, we observed autophagic perturbations and an enlargement of the lysosomal compartment specifically in dopamine neurons. Finally, we found increased extracellular α-synuclein in patient-derived neuronal culture medium, which was not associated with exosomes. Overall, ER stress, autophagic/lysosomal perturbations, and elevated extracellular α-synuclein likely represent critical early cellular phenotypes of PD, which might offer multiple therapeutic targets.
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Cites
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894
Self-citationControl of inositol 1,4,5-trisphosphate-induced Ca2+ release by cytosolic Ca2+
Bootman, M. D., Missiaen, L., Parys, J. B., De Smedt, H., & Casteels, R. (1995) · Biochemical Journal · doi:10.1042/bj3060445 · Cited by 5,120
Guidelines for the use and interpretation of assays for monitoring autophagy
Klionsky, D. J., Abdalla, F. C., Abeliovich, H., Abraham, R. T., Acevedo-Arozena, A., Adeli, K., Agholme, L., Agnello, M., Agostinis, P., Aguirre-Ghiso, J. A., et al. (2012) · Autophagy · doi:10.4161/auto.19496 · Cited by 3,996 · cited 6×
“346 Stem Cell Reports j Vol. 6 j 342–356 j March 8, 2016 j ª2016 The Autho Impaired Lysosomal Degradation in GBA-N370S Dopaminergic Neurons Accumulation of autophagosomes can also reflect a defect in lysosomal clearance (Klionsky et al., 2012).”
BackgroundInfluentialSelf-citationMulticenter Analysis of Glucocerebrosidase Mutations in Parkinson's Disease
Sidransky, E., Nalls, M. A., Aasly, J. O., Aharon-Peretz, J., Annesi, G., Barbosa, E. R., Bar-Shira, A., Berg, D., Bras, J., Brice, A., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0901281 · Cited by 2,135
Impaired Degradation of Mutant α-Synuclein by Chaperone-Mediated Autophagy
Cuervo, A. M., Stefanis, L., Fredenburg, R., Lansbury, P. T., & Sulzer, D. (2004) · Science · doi:10.1126/science.1101738 · Cited by 2,024 · cited 3×
“…in this context might be complex since it was also previously shown to cause ER stress, block ER-Golgi trafficking (Cooper et al., 2006), induce lysosomal rupture (Freeman et al., 2013), decrease lysosomal function (Cuervo et al., 2004), and inhibit GCase activity (Mazzulli et al., 2011).”
BackgroundInclusion formation and neuronal cell death through neuron-to-neuron transmission of α-synuclein
Desplats, P., Lee, H.-J., Bae, E.-J., Patrick, C., Rockenstein, E., Crews, L., Spencer, B., Masliah, E., & Lee, S.-J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903691106 · Cited by 1,485
α-Synuclein Blocks ER-Golgi Traffic and Rab1 Rescues Neuron Loss in Parkinson's Models
Cooper, A. A., Gitler, A. D., Cashikar, A., Haynes, C. M., Hill, K. J., Bhullar, B., Liu, K., Xu, K., Strathearn, K. E., Liu, F., et al. (2006) · Science · doi:10.1126/science.1129462 · Cited by 1,376
Mazzulli, J. R., Xu, Y.-H., Sun, Y., Knight, A. L., McLean, P. J., Caldwell, G. A., Sidransky, E., Grabowski, G. A., & Krainc, D. (2011) · Cell · doi:10.1016/j.cell.2011.06.001 · Cited by 1,341
Emmanouilidou, E., Melachroinou, K., Roumeliotis, T., Garbis, S. D., Ntzouni, M., Margaritis, L. H., Stefanis, L., & Vekrellis, K. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5699-09.2010 · Cited by 1,115 · cited 4×
“In addition, although earlier reports showed that a-synuclein release was independent of the ER/Golgi classical export pathway (Emmanouilidou et al., 2010; Jang et al., 2010; Lee et al., 2005), recent studies have shown that in some models, including enteric neurons, a-synuclein release is…”
BackgroundResultInfluentialSelf-citationEndoplasmic Reticulum Stress Triggers Autophagy
Yorimitsu, T., Nair, U., Yang, Z., & Klionsky, D. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m607007200 · Cited by 951
Cited by
Poewe, W., Seppi, K., Tanner, C. M., Halliday, G. M., Brundin, P., Volkmann, J., Schrag, A.-E., & Lang, A. E. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.13 · Cited by 5,415
Inflammation and immune dysfunction in Parkinson disease
Tansey, M. G., Wallings, R. L., Houser, M. C., Herrick, M. K., Keating, C. E., & Joers, V. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-022-00684-6 · Cited by 1,382
ER stress and the unfolded protein response in neurodegeneration
Hetz, C., & Saxena, S. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.99 · Cited by 1,013
The Role of Autophagy in Parkinson's Disease
Lynch-Day, M. A., Mao, K., Wang, K., Zhao, M., & Klionsky, D. J. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009357 · Cited by 458
Schöndorf, D. C., Ivanyuk, D., Baden, P., Sanchez-Martinez, A., De Cicco, S., Yu, C., Giunta, I., Schwarz, L. K., Di Napoli, G., Panagiotakopoulou, V., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.05.009 · Cited by 337
Metadata
- Authors
- Fernandes, H. J. R., Hartfield, E. M., Christian, H. C., Emmanoulidou, E., Zheng, Y., Booth, H., Bogetofte, H., Lang, C., Ryan, B. J., Sardi, S. P., Badger, J., Vowles, J., Evetts, S., Tofaris, G. K., Vekrellis, K., Talbot, K., Hu, M. T., James, W., Cowley, S. A., & Wade-Martins, R.
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 6
- Issue
- 3
- Pages
- 342-356
- ISSN
- 2213-6711 (ISSN-L)
- OpenAlex
- W2277130721
- Cited by
- 351
- References
- 49
- FWCI
- 24.18
- Type
- journal article
- Language
- en
- Open access
- gold
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- CoChat. (2026). Citation check: ER Stress and Autophagic Perturbations Lead to Elevated Extracellular α-Synuclein in GBA-N370S Parkinson's iPSC-Derived Dopamine Neurons. https://app.cochat.ai/papers/10.1016/j.stemcr.2016.01.013
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- Fernandes, H. J. R., Hartfield, E. M., Christian, H. C., Emmanoulidou, E., Zheng, Y., Booth, H., Bogetofte, H., Lang, C., Ryan, B. J., Sardi, S. P., Badger, J., Vowles, J., Evetts, S., Tofaris, G. K., Vekrellis, K., Talbot, K., Hu, M. T., James, W., Cowley, S. A., & Wade-Martins, R. (2016). ER Stress and Autophagic Perturbations Lead to Elevated Extracellular α-Synuclein in GBA-N370S Parkinson's iPSC-Derived Dopamine Neurons. Stem Cell Reports. https://doi.org/10.1016/j.stemcr.2016.01.013
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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