Tau protein is a natively unfolded protein whose primary role is to participate in axonal transport closely associated with microtubules. Neurodegenerative disorders including Alzheimer's disease and Tauopathies involved tau protein that is found hyperphosphorylated in vivo ; then, tau is detached from microtubules to form toxic aggregates or oligomers, which have a deleterious effect on membranes, triggering an inflammatory response. Considering finding tau inhibitors, we isolated two compounds in the ethyl acetate extract from Xanthoria ectaneoides (Nyl.) Zahlbr; ergosterol peroxide ( 1 ) and a new anthraquinone ( 2 ). We established the structure through spectroscopic data and biogenic considerations, and we named it “2‐hydroxy‐3‐((8‐hydroxy‐3‐methoxy‐6‐methylanthraquinonyl)oxy)propanoic acid”. This new anthraquinone was evaluated as a tau inhibitor by ThT fluorescence, dot blot assays and total internal reflection fluorescence microscopy. Our results strongly suggest that this anthraquinone remodels soluble oligomers and diminishes β‐sheet content. Moreover, through the fluorescence labeling of cysteine inside of the microtubule‐binding domain (4R), we showed that this anthraquinone could reduce the oligomers progression by inhibiting cysteine interactions.

The Cover Feature shows a new derivative anthraquinone isolated from Lichen Xanthoria ectaneoides (Nyl.) Zahlbr, which can reduce progression of oligomers of tau protein involved in neurodegenerative disorders such as Tauopathies. Considering that adults are increasing in number and that current treatments are only palliative, it is crucial to considerer new compounds as a scaffold for drug development. More information can be found in the Communication by C. Areche et al. on page 554 in Issue 5, 2019 (DOI: 10.1002/open.201800222).