Correction: Defining α-synuclein species responsible for Parkinson's disease phenotypes in mice.

Froula, Jessica M.; Castellana-Cruz, Marta; Anabtawi, Nadia M.; Camino, José D.; Chen, Serene W.; Thrasher, Drake R.; Freire, Jennifer; Yazdi, Allen A.; Fleming, Sheila M.; Dobson, Christopher M.; Kumita, Janet R.; Cremades, Nunilo; Volpicelli‐Daley, Laura A.

doi:10.1016/s0021-9258(17)49921-2

Cited by 2 publications

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“…It remains to be seen whether our approach in tissular substrates may be used for the study of human diseases and/or other experimental models of synucleinopathies. However, our results importantly demonstrate for the first time that pathogenic properties can be induced after an in vitro amplification from pathologic α‐syn seeds, which can now be studied in other experimental models, including nontransgenic animals (45). The sonication‐based PMCA approach in a brain substrate may help in deciphering the molecular basis of α‐syn aggregation in a physiologically relevant environment, including the assessment of aggregation‐inhibitory molecules with potential therapeutic applications (46) or, more basically, to better understand unresolved questions in the field such as the possible existence of α‐syn strains (10, 17, 47, 48).…”

Section: Discussionmentioning

confidence: 71%

Seeded propagation of α‐synuclein aggregation in mouse brain using protein misfolding cyclic amplification

et al. 2019

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α‐Synuclein (α‐syn) protein aggregation is associated with several neurodegenerative disorders collectively referred to as synucleinopathies, including Parkinson's disease. We used protein misfolding cyclic amplification (PMCA) to study α‐syn aggregation in brain homogenates of wild‐type or transgenic mice expressing normal (D line) or A53T mutant (M83 line) human α‐syn. We found that sonication‐incubation cycles of M83 mouse brain gradually produce large quantities of SDS‐resistant α‐syn aggregates, involving both human and mouse proteins. These PMCA products, containing partially proteinase K‐resistant α‐syn species, are competent to accelerate the onset of neurologic symptoms after intracerebral inoculation to young M83 mice and to seed aggregate formation of α‐syn following PMCA, including in D and wild‐type mouse brain substrates. PMCA seeding activity in the M83 diseased brain correlates positively with regions mostly targeted by the α‐syn pathology in this model. Our data indicate that similar to prions, PMCA can reproduce some characteristics of α‐syn aggregation and seeded propagation in vitro in a complex milieu. This opens new opportunities for the molecular study of synucleinopathies.—Nicot, S., Verchère, J., Bélondrade, M., Mayran, C., Bétemps, D., Bougard, D., Baron, T. Seeded propagation of α‐synuclein aggregation in mouse brain using protein misfolding cyclic amplification. FASEB J. 33, 12073‐12086 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 71%

Seeded propagation of α‐synuclein aggregation in mouse brain using protein misfolding cyclic amplification

et al. 2019

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Multiplicity of α-Synuclein Aggregated Species and Their Possible Roles in Disease

Gracia

Camino

Volpicelli‐Daley

et al. 2020

IJMS

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α-Synuclein amyloid aggregation is a defining molecular feature of Parkinson’s disease, Lewy body dementia, and multiple system atrophy, but can also be found in other neurodegenerative disorders such as Alzheimer’s disease. The process of α-synuclein aggregation can be initiated through alternative nucleation mechanisms and dominated by different secondary processes giving rise to multiple amyloid polymorphs and intermediate species. Some aggregated species have more inherent abilities to induce cellular stress and toxicity, while others seem to be more potent in propagating neurodegeneration. The preference for particular types of polymorphs depends on the solution conditions and the cellular microenvironment that the protein encounters, which is likely related to the distinct cellular locations of α-synuclein inclusions in different synucleinopathies, and the existence of disease-specific amyloid polymorphs. In this review, we discuss our current understanding on the nature and structure of the various types of α-synuclein aggregated species and their possible roles in pathology. Precisely defining these distinct α-synuclein species will contribute to understanding the molecular origins of these disorders, developing accurate diagnoses, and designing effective therapeutic interventions for these highly debilitating neurodegenerative diseases.

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Correction: Defining α-synuclein species responsible for Parkinson's disease phenotypes in mice.

Cited by 2 publications

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Seeded propagation of α‐synuclein aggregation in mouse brain using protein misfolding cyclic amplification

Seeded propagation of α‐synuclein aggregation in mouse brain using protein misfolding cyclic amplification

Multiplicity of α-Synuclein Aggregated Species and Their Possible Roles in Disease

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