Alkannin Attenuates Amyloid β Aggregation and Alzheimer's Disease Pathology

Toru Hosoi*, Kyosuke Yazawa, Michihiro Imada, Akari Tawara, Chihiro Tohda, Yasuyuki Nomura, Koichiro Ozawa*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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 b 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 b-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.

Original languageEnglish
Pages (from-to)266-273
Number of pages8
JournalMolecular Pharmacology
Volume103
Issue number5
DOIs
StatePublished - 2023/05/01

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint

Dive into the research topics of 'Alkannin Attenuates Amyloid β Aggregation and Alzheimer's Disease Pathology'. Together they form a unique fingerprint.

Cite this