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Lysosomal Degradation of α-Synuclein in Vivo
Open accessAbstract
Pathologic accumulation of alpha-synuclein is a feature of human parkinsonism and other neurodegenerative diseases. This accumulation may be counteracted by mechanisms of protein degradation that have been investigated in vitro but remain to be elucidated in animal models. In this study, lysosomal clearance of alpha-synuclein in vivo was indicated by the detection of alpha-synuclein in the lumen of lysosomes isolated from the mouse midbrain. When neuronal alpha-synuclein expression was enhanced as a result of toxic injury (i.e. treatment of mice with the herbicide paraquat) or transgenic protein overexpression, the intralysosomal content of alpha-synuclein was also significantly increased. This effect was paralleled by a marked elevation of the lysosome-associated membrane protein type 2A (LAMP-2A) and the lysosomal heat shock cognate protein of 70 kDa (hsc70), two essential components of chaperone-mediated autophagy (CMA). Immunofluorescence microscopy revealed an increase in punctate (lysosomal) LAMP-2A staining that co-localized with alpha-synuclein within nigral dopaminergic neurons of paraquat-treated and alpha-synuclein-overexpressing animals. The data provide in vivo evidence of lysosomal degradation of alpha-synuclein under normal conditions and, quite importantly, under conditions of enhanced protein burden. In the latter, increased lysosomal clearance of alpha-synuclein was mediated, at least in part, by CMA induction. It is conceivable that these neuronal mechanisms of protein clearance play an important role in neurodegenerative processes characterized by abnormal alpha-synuclein buildup.
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Cites
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
Self-citationα-Synuclein Is Degraded by Both Autophagy and the Proteasome
Webb, J. L., Ravikumar, B., Atkins, J., Skepper, J. N., & Rubinsztein, D. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300227200 · Cited by 1,429
Vogiatzi, T., Xilouri, M., Vekrellis, K., & Stefanis, L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801992200 · Cited by 683
Consequences of the selective blockage of chaperone-mediated autophagy
Massey, A. C., Kaushik, S., Sovak, G., Kiffin, R., & Cuervo, A. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507436103 · Cited by 529
Self-citationClearance of α-Synuclein Oligomeric Intermediates via the Lysosomal Degradation Pathway
Lee, H.-J., Khoshaghideh, F., Patel, S., & Lee, S.-J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.3809-03.2004 · Cited by 445
Yu, W. H., Dorado, B., Figueroa, H. Y., Wang, L., Planel, E., Cookson, M. R., Clark, L. N., & Duff, K. E. (2009) · The American Journal of Pathology · doi:10.2353/ajpath.2009.080928 · Cited by 155
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-Synuclein in Parkinson's Disease
Stefanis, L. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009399 · Cited by 1,446
The coming of age of chaperone-mediated autophagy
Kaushik, S., & Cuervo, A. M. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0001-6 · Cited by 1,407
Self-citationBendor, J. T., Logan, T. P., & Edwards, R. H. (2013) · Neuron · doi:10.1016/j.neuron.2013.09.004 · Cited by 825
TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity
Decressac, M., Mattsson, B., Weikop, P., Lundblad, M., Jakobsson, J., & Björklund, A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1305623110 · Cited by 753
Interplay of LRRK2 with chaperone-mediated autophagy
Orenstein, S. J., Kuo, S.-H., Tasset, I., Arias, E., Koga, H., Fernandez-Carasa, I., Cortes, E., Honig, L. S., Dauer, W., Consiglio, A., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3350 · Cited by 588
Self-citationA Guide to Neurotoxic Animal Models of Parkinson's Disease
Tieu, K. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009316 · Cited by 483
Tunneling nanotubes spread fibrillar α-synuclein by intercellular trafficking of lysosomes
Abounit, S., Bousset, L., Loria, F., Zhu, S., de Chaumont, F., Pieri, L., Olivo‐Marin, J., Melki, R., & Zurzolo, C. (2016) · The EMBO Journal · doi:10.15252/embj.201593411 · Cited by 414
α-synuclein in the pathophysiology of Alzheimer’s disease
Twohig, D., & Nielsen, H. M. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0320-x · Cited by 374
Lysosomal impairment in Parkinson's disease
Dehay, B., Martinez‐Vicente, M., Caldwell, G. A., Caldwell, K. A., Yue, Z., Cookson, M. R., Klein, C., Vila, M., & Bezard, E. (2013) · Movement Disorders · doi:10.1002/mds.25462 · Cited by 340
Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome
Bourdenx, M., Martín-Segura, A., Scrivo, A., Rodriguez-Navarro, J. A., Kaushik, S., Tasset, I., Diaz, A., Storm, N. J., Xin, Q., Juste, Y. R., et al. (2021) · Cell · doi:10.1016/j.cell.2021.03.048 · Cited by 337
Self-citationUbiquitin ligase Nedd4 promotes α-synuclein degradation by the endosomal–lysosomal pathway
Tofaris, G. K., Kim, H. T., Hourez, R., Jung, J.-W., Kim, K. P., & Goldberg, A. L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1109356108 · Cited by 271
Tang, F.-L., Erion, J. R., Tian, Y., Liu, W., Yin, D.-M., Ye, J., Tang, B., Mei, L., & Xiong, W.-C. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0042-15.2015 · Cited by 269
Anionic nanoplastic contaminants promote Parkinson’s disease–associated α-synuclein aggregation
Liu, Z., Sokratian, A., Duda, A. M., Xu, E., Stanhope, C., Fu, A., Strader, S., Li, H., Yuan, Y., Bobay, B. G., et al. (2023) · Science Advances · doi:10.1126/sciadv.adi8716 · Cited by 262
Genetic perspective on the role of the autophagy-lysosome pathway in Parkinson disease
Gan-Or, Z., Dion, P. A., & Rouleau, G. A. (2015) · Autophagy · doi:10.1080/15548627.2015.1067364 · Cited by 260
Lindström, V., Gustafsson, G., Sanders, L. H., Howlett, E. H., Sigvardson, J., Kasrayan, A., Ingelsson, M., Bergström, J., & Erlandsson, A. (2017) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2017.04.009 · Cited by 233
Microglia affect α-synuclein cell-to-cell transfer in a mouse model of Parkinson’s disease
George, S., Rey, N. L., Tyson, T., Esquibel, C., Meyerdirk, L., Schulz, E., Pierce, S., Burmeister, A. R., Madaj, Z., Steiner, J. A., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0335-3 · Cited by 229
Chemical modulation of chaperone-mediated autophagy by retinoic acid derivatives
Anguiano, J., Garner, T. P., Mahalingam, M., Das, B. C., Gavathiotis, E., & Cuervo, A. M. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1230 · Cited by 222
Self-citationExosomal secretion of α-synuclein as protective mechanism after upstream blockage of macroautophagy
Fussi, N., Höllerhage, M., Chakroun, T., Nykänen, N.-P., Rösler, T. W., Koeglsperger, T., Wurst, W., Behrends, C., & Höglinger, G. U. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-0816-2 · Cited by 161
The Role of Cathepsin D in the Pathogenesis of Human Neurodegenerative Disorders
Vidoni, C., Follo, C., Savino, M., Melone, M. A. B., & Isidoro, C. (2016) · Medicinal Research Reviews · doi:10.1002/med.21394 · Cited by 164
Kim, C., Spencer, B., Rockenstein, E., Yamakado, H., Mante, M., Adame, A., Fields, J. A., Masliah, D., Iba, M., Lee, H.-J., et al. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0276-2 · Cited by 157
Schildknecht, S., Gerding, H. R., Karreman, C., Drescher, M., Lashuel, H. A., Outeiro, T. F., Di Monte, D. A., & Leist, M. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12226 · Cited by 148
Chaperone-mediated autophagy. Machinery, regulation and biological consequences
Li, W., Yang, Q., & Mao, Z. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0565-6 · Cited by 119
Import and Export of Misfolded α-Synuclein
Rodriguez, L., Marano, M. M., & Tandon, A. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00344 · Cited by 93
Chaperone mediated autophagy degrades TDP-43 protein and is affected by TDP-43 aggregation
Ormeño, F., Hormazabal, J., Moreno, J., Riquelme, F., Rios, J., Criollo, A., Albornoz, A., Alfaro, I. E., & Budini, M. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00019 · Cited by 80
Su, C., Yang, X., & Lou, J. (2016) · Brain Research · doi:10.1016/j.brainres.2016.05.011 · Cited by 75
Vulnerability of mesostriatal dopaminergic neurons in Parkinson’s disease
González-Hernández, T. (2010) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2010.00140 · Cited by 65
Michelakakis, H., Xiromerisiou, G., Dardiotis, E., Bozi, M., Vassilatis, D., Kountra, P., Patramani, G., Moraitou, M., Papadimitriou, D., Stamboulis, E., et al. (2012) · Movement Disorders · doi:10.1002/mds.24886 · Cited by 64
Limegrover, C. S., Yurko, R., Izzo, N. J., LaBarbera, K. M., Rehak, C., Look, G., Rishton, G., Safferstein, H., & Catalano, S. M. (2021) · Journal of Neuroscience Research · doi:10.1002/jnr.24782 · Cited by 43
What lysosomes actually tell us about Parkinson’s disease?
Bourdenx, M., & Dehay, B. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.02.008 · Cited by 26
Metadata
- Authors
- Mak, S. K., McCormack, A. L., Manning-Boğ, A. B., Cuervo, A. M., & Di Monte, D. A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 285
- Issue
- 18
- Pages
- 13621-13629
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1993467627
- Cited by
- 349
- References
- 6
- FWCI
- 16.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
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