doi:10.1038/s41467-022-32350-9engGracia, PabloPolanco, DavidTarancón-Díez, JorgeSerra, IleniaBracci, MaruanOroz, JavierLaurents, Douglas V.García-Rubio, InésCremades, NuniloMolecular mechanism for the synchronized electrostatic coacervation and co-aggregation of a-synuclein and tauART-2022-129511Amyloid aggregation of α-synuclein (αS) is the hallmark of Parkinson’s disease and other synucleinopathies. Recently, Tau protein, generally associated with Alzheimer’s disease, has been linked to αS pathology and observed to co- localize in αS-rich disease inclusions, although the molecular mechanisms for the co-aggregation of both proteins remain elusive. We report here that αS phase-separates into liquid condensates by electrostatic complex coacerva- tion with positively charged polypeptides such as Tau. Condensates undergo either fast gelation or coalescence followed by slow amyloid aggregation depending on the affinity of αS for the poly-cation and the rate of valence exhaustion of the condensate network. By combining a set of advanced bio- physical techniques, we have been able to characterize αS/Tau liquid-liquid phase separation and identified key factors that lead to the formation of hetero-aggregates containing both proteins in the interior of the liquid protein condensates.2022http://zaguan.unizar.es/record/11801310.1038/s41467-022-32350-9http://zaguan.unizar.es/record/118013oai:zaguan.unizar.es:118013info:eu-repo/grantAgreement/EC/H2020/813209/EU/Paramagnetic Species in Catalysis Research. A Unified Approach Towards Heterogeneous, Homogeneous and Enzyme Catalysis/PARACATThis project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 813209-PARACATinfo:eu-repo/grantAgreement/ES/MICINN-AEI/PGC2018-096335-B100info:eu-repo/grantAgreement/ES/MICINN-AEI/PID2019-109276RA-I00info:eu-repo/grantAgreement/ES/MICINN-AEI/PID2019-109306RB-I00info:eu-repo/grantAgreement/ES/MICINN/RYC2018-026042-Iinfo:eu-repo/grantAgreement/ES/UZ/CUD2019-BIO-01info:eu-repo/grantAgreement/ES/UZ/CUD2020-BIO-01Nature communications 13 (2022), 4586 [16 pp.]byhttp://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccess