@article{de_giorgi_novel_2020,
	title = {Novel self-replicating α-synuclein polymorphs that escape {ThT} monitoring can spontaneously emerge and acutely spread in neurons},
	volume = {6},
	issn = {2375-2548},
	url = {https://advances.sciencemag.org/lookup/doi/10.1126/sciadv.abc4364},
	doi = {10.1126/sciadv.abc4364},
	abstract = {The conformational strain diversity characterizing α-synuclein (α-syn) amyloid fibrils is thought to determine the different clinical presentations of neurodegenerative diseases underpinned by a synucleinopathy. Experimentally, various α-syn fibril polymorphs have been obtained from distinct fibrillization conditions by altering the medium constituents and were selected by amyloid monitoring using the probe thioflavin T (ThT). We report that, concurrent with classical ThT-positive products, fibrillization in saline also gives rise to polymorphs invisible to ThT (τ
              −
              ). The generation of τ
              −
              fibril polymorphs is stochastic and can skew the apparent fibrillization kinetics revealed by ThT. Their emergence has thus been ignored so far or mistaken for fibrillization inhibitions/failures. They present a yet undescribed atomic organization and show an exacerbated propensity toward self-replication in cortical neurons, and in living mice, their injection into the substantia nigra pars compacta triggers a synucleinopathy that spreads toward the dorsal striatum, the nucleus accumbens, and the insular cortex.},
	language = {en},
	number = {40},
	urldate = {2021-02-24},
	journal = {Science Advances},
	author = {De Giorgi, Francesca and Laferrière, Florent and Zinghirino, Federica and Faggiani, Emilie and Lends, Alons and Bertoni, Mathilde and Yu, Xuan and Grélard, Axelle and Morvan, Estelle and Habenstein, Birgit and Dutheil, Nathalie and Doudnikoff, Evelyne and Daniel, Jonathan and Claverol, Stéphane and Qin, Chuan and Loquet, Antoine and Bezard, Erwan and Ichas, François},
	month = oct,
	year = {2020},
	keywords = {highlight, peer-reviewed},
	pages = {eabc4364},
}