Liquid-liquid phase separation of tau is demonstrated to be an equilibrium state, stable only within a narrow range near physiological conditions, and thus has the capacity to regulate biological processes.
Pathogenesis in Spinocerebellar Ataxia Type 3 is enhanced by the heat-shock protein family member, Hsc70-4, uncovering new mechanisms of toxicity for this disease and suggesting pleiotropic roles for chaperones.
One α-synuclein strain inhibited proteasome activity and induced apparent pathologies, while the other did not, indicating a strain-dependent toxicity of α-synuclein aggregates, which support a prion-like behavior of α-synuclein.
Tau monomer from aggregate-containing cell models and tauopathy brains adopts discrete structures that act as templates, dictating the conformation of distinct strains that result from its seeding activity.
A novel auto-inhibitory mechanism regulates the functional activity of the cellular prion protein, PrPC, providing for the first time a coherent molecular model for both its pathological and physiological effects.