PT - JOURNAL ARTICLE AU - Hosoi, Toru AU - Yazawa, Kyosuke AU - Imada, Michihiro AU - Tawara, Akari AU - Tohda, Chihiro AU - Nomura, Yasuyuki AU - Ozawa, Koichiro TI - Alkannin Attenuates Amyloid <em>β</em> Aggregation and Alzheimer’s Disease Pathology AID - 10.1124/molpharm.121.000468 DP - 2023 May 01 TA - Molecular Pharmacology PG - 266--273 VI - 103 IP - 5 4099 - http://molpharm.aspetjournals.org/content/103/5/266.short 4100 - http://molpharm.aspetjournals.org/content/103/5/266.full SO - Mol Pharmacol2023 May 01; 103 AB - Alzheimer’s disease (AD) is a neurodegenerative disease that is accompanied by memory decline and cognitive dysfunction. Aggregated amyloid β formation and accumulation may be one of the underlying mechanisms of the pathophysiology of AD. Therefore, compounds that can inhibit amyloid β aggregation may be useful for treatment. Based on this hypothesis, we screened plant compounds used in Kampo medicine for chemical chaperone activity and identified that alkannin had this property. Further analysis indicated that alkannin could inhibit amyloid β aggregation. Importantly, we also found that alkannin inhibited amyloid β aggregation after aggregates had already formed. Through the analysis of circular dichroism spectra, alkannin was found to inhibit β-sheet structure formation, which is an aggregation-prone toxic structure. Furthermore, alkannin attenuated amyloid β-induced neuronal cell death in PC12 cells, ameliorated amyloid β aggregation in the AD model of Caenorhabditis elegans (C. elegans), and inhibited chemotaxis observed in AD C. elegans, suggesting that alkannin could potentially inhibit neurodegeneration in vivo. Overall, these results suggest that alkannin may have novel pharmacological properties for inhibiting amyloid β aggregation and neuronal cell death in AD.SIGNIFICANCE STATEMENT Aggregated amyloid β formation and accumulation is one of the underlying mechanisms of the pathophysiology of Alzheimer’s disease. We found that alkannin had chemical chaperone activity, which can inhibit β-sheet structure formation of amyloid β and its aggregation, neuronal cell death, and Alzheimer’s disease phenotype in C. elegans. Overall, alkannin may have novel pharmacological properties for inhibiting amyloid β aggregation and neuronal cell death in Alzheimer’s disease.