
@article {78265,
	title = {α-Synuclein aggregation nucleates through liquid-liquid phase separation.},
	journal = {Nat Chem},
	year = {2020},
	month = {2020 Jun 08},
	abstract = {<p>α-Synuclein (α-Syn) aggregation and amyloid formation is directly linked with Parkinson{\textquoteright}s disease pathogenesis. However, the early events involved in this process remain unclear. Here, using the in vitro reconstitution and cellular model, we show that liquid-liquid phase separation of α-Syn precedes its aggregation. In particular, in vitro generated α-Syn liquid-like droplets eventually undergo a liquid-to-solid transition and form an amyloid hydrogel that contains oligomers and fibrillar species. Factors known to aggravate α-Syn aggregation, such as low pH, phosphomimetic substitution and familial Parkinson{\textquoteright}s disease mutations, also promote α-Syn liquid-liquid phase separation and its subsequent maturation. We further demonstrate α-Syn liquid-droplet formation in cells. These cellular α-Syn droplets eventually transform into perinuclear aggresomes, the process regulated by microtubules. This work provides detailed insights into the phase-separation behaviour of natively unstructured α-Syn and its conversion to a disease-associated aggregated state, which is highly relevant in Parkinson{\textquoteright}s disease pathogenesis.</p>
},
	issn = {1755-4349},
	doi = {10.1038/s41557-020-0465-9},
	author = {Ray, Soumik and Singh, Nitu and Kumar, Rakesh and Patel, Komal and Pandey, Satyaprakash and Datta, Debalina and Mahato, Jaladhar and Panigrahi, Rajlaxmi and Navalkar, Ambuja and Mehra, Surabhi and Gadhe, Laxmikant and Chatterjee, Debdeep and Sawner, Ajay Singh and Maiti, Siddhartha and Bhatia, Sandhya and Gerez, Juan Atilio and Chowdhury, Arindam and Kumar, Ashutosh and Padinhateeri, Ranjith and Riek, Roland and Krishnamoorthy, G and Maji, Samir K}
}
