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

By Kelvin C. Luk, Cheng Song, Patrick O’Brien, Anna Stieber, Jonathan R. Branch, K. Brunden, John Q. Trojanowski, V. Lee. Proceedings of the National Academy of Sciences of the United States of America, 2009

942 citations recorded by the source corpus.

Subfields: Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/7cd766b93712c3b25410b225fa0907864fa89626

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Neurology

1. V. Lee
2. Leonidas Stefanis
3. John Q. Trojanowski
4. Kelvin C. Luk
5. Bin Zhang
6. L. Volpicelli-Daley
7. H. Ko
8. D. Selkoe

In Physiology

1. V. Lee
2. John Q. Trojanowski
3. Bin Zhang
4. Leonidas Stefanis
5. Kelvin C. Luk
6. H. Ko
7. E. Mandelkow
8. M. Goedert

Citations in the corpus

• Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats (2014, background): “In vitro studies with microfluidic chambers showed that preformed α-synuclein fibrils were not only taken up and transported within primary neurons but also transmitted to secondary neurons [13, 33].”
• Exosomal cell-to-cell transmission of alpha synuclein oligomers (2012, background): “In support of this hypothesis, recombinant αsyn oligomers added to cell culture medium have been shown to be internalized by recipient cells causing either cell death or seeding of αsyn [18-22].”
• α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. (2011, neutral): “The seeding effect of α -syn has previously been suggested, albeit in artificial systems using liposome-based delivery of α -syn fibrils (31) or addition of a certain type of recombinant oligo-meric α -syn to the culture medium at high concentrations (32), in contrast to our more physiologically…”
• Cell-Produced α-Synuclein Is Secreted in a Calcium-Dependent Manner by Exosomes and Impacts Neuronal Survival (2010, background): “In support for this hypothesis, exogenously added recombinant -synuclein to cell culture medium can be internalized by the recipient cells (Sung et al., 2001; Ahn et al., 2006; Lee et al., 2008; Luk et al., 2009) and cause cell death (Du et al.”
• Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson's Disease. (2019, background): “These preformed fibrils (PFF) can spread in prionlike manner both in in vitro neuronal cultures as well as in vivo when injected into the mouse brain, forming pSer129-a-syn-positive LB-like inclusions (Luk et al., 2009, 2012).”
• Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds (2013, background): “(2007) beta-Sheet structured beta-amyloid(1-40) perturbs phosphatidylcholine model membranes.”
• α-Synuclein in Parkinson's disease. (2012, background): “Oligomeric-aggregated a-synuclein species appear to be especially prone to uptake and have the potential to “seed” fibrillization of endogenous a-synuclein (Danzer et al. 2007, 2009, 2011; Luk et al. 2009; Nonaka et al. 2010; Waxman and Giasson 2010; Hansen et al. 2011).”