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The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Exogenous α-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells

Luk, Kelvin C., Song, Cheng, O'Brien, Patrick, Stieber, Anna, Branch, Jonathan R., Brunden, Kurt R., Trojanowski, John Q., Lee, Virginia M.-Y.·2009·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0908005106
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Abstract

Cytoplasmic inclusions containing α-synuclein (α-Syn) fibrils, referred to as Lewy bodies (LBs), are the signature neuropathological hallmarks of Parkinson's disease (PD). Although α-Syn fibrils can be generated from recombinant α-Syn protein in vitro, the production of fibrillar α-Syn inclusions similar to authentic LBs in cultured cells has not been achieved. We show here that intracellular α-Syn aggregation can be triggered by the introduction of exogenously produced recombinant α-Syn fibrils into cultured cells engineered to overexpress α-Syn. Unlike unassembled α-Syn, these α-Syn fibrils “seeded” recruitment of endogenous soluble α-Syn protein and their conversion into insoluble, hyperphosphorylated, and ubiquitinated pathological species. Thus, this cell model recapitulates key features of LBs in human PD brains. Also, these findings support the concept that intracellular α-Syn aggregation is normally limited by the number of active nucleation sites present in the cytoplasm and that small quantities of α-Syn fibrils can alter this balance by acting as seeds for aggregation.

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  • Oligomeric α-Syn species appear prone to uptake and spread from cell-to-cell in a prion-like manner, leading to templated misfolding of native α-Syn and formation of aggregates throughout the brain.

    “Particularly, the oligomeric α-Syn species appear to be prone to uptake and spread from cell-to-cell in a prion-like manner, leading to the templated misfolding of the native forms of α-Syn and formation of α-Syn aggregates throughout the brain, which are the defining pathological features of Parkinson’s disease (PD) and dementia with Lewy body (DLB) [12–19].”

    From LRP1 is a neuronal receptor for α-synuclein uptake and spread (2022) · cites this paper as [17]

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Research works printed but not linked: 21

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  16. M Baba, et al., Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies. Am J Pathol 152, 879–884 (1998).
  17. 10.1091/mbc.e07-08-0827 · DOI
  18. 10.1126/science.1129462 · DOI
  19. 10.1126/science.1090278 · DOI · Paper page
  20. 10.1073/pnas.0406976102 · DOI
  21. H Braak, K Del Tredici, Neuroanatomy and pathology of sporadic Parkinson's disease. Adv Anat Embryol Cell Biol 201, 1–119 (2009).

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Metadata

Authors
Luk, K. C., Song, C., O'Brien, P., Stieber, A., Branch, J. R., Brunden, K. R., Trojanowski, J. Q., & Lee, V. M.-Y.
Affiliations
Center for Neurodegenerative Disease Research, Institute on Aging, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2009-11-24
Volume
106
Issue
47
Pages
20051-20056
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.0908005106
Cited by
938
References
6
Language
en

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