Cinnamon Bud Extract Is a Source of Biomolecules Active against the Aggregation and Condensation of Alzheimer′s-Associated Tau Protein

High Resolution Image Download MS PowerPoint Slide Abnormal accumulation of tau fibrillar aggregates is a hallmark of tauopathies, including Alzheimer’s disease. Targeting tau aggregation represents a promising strategy for preventing and treating neurological disorders, especially using natural compounds with favorable safety profiles. In this study, we investigated a hydroalcoholic extract of Cinnamomum cassia buds (BCHE) and its major components, cinnamaldehyde and shikimic acid, for their effects in modulating tau repeat domain aggregation and liquid–liquid phase separation. In vitro results show that BCHE and cinnamaldehyde inhibit tau aggregate maturation, promoting the formation of nonfibrillar, off-pathway species and modulating condensate formation. These alternative aggregates exhibit reduced cytotoxicity in SH-SY5Y neuroblastoma cells and lower seeding capacity than canonical fibrils. BCHE also contains compounds capable of binding preformed tau fibrils. Overall, these findings suggest a novel mechanism by which cinnamon-derived bioactive molecules mitigate tau aggregation and reduce its cellular toxicity, highlighting their potential as neuroprotective agents.