Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Mar;179(5):1033-1048.
doi: 10.1111/bph.15691. Epub 2021 Nov 4.

The potential anti-amyloidogenic candidate, SPA1413, for Alzheimer's disease

Seong Soo A An  1 , Kyu Hwan Shim  1   2 , Shinwoo Kang  3   4 , Young Kyo Kim  5 , Lalita Subedi  6 , Hyewon Cho  7 , Seong-Min Hong  6 , Mario A Tan  1   8 , Raok Jeon  7 , Keun-A Chang  3   4   5 , Sun Yeou Kim  6
Affiliations
Free article

The potential anti-amyloidogenic candidate, SPA1413, for Alzheimer's disease

Seong Soo A An et al. Br J Pharmacol. 2022 Mar.
Free article

Abstract

Background and purpose: Recently, isoflavone derivatives have been shown to have neuroprotective effects against neurological disorders. For instance, genistein attenuated the neuroinflammation and amyloid-β accumulation in Alzheimer's disease animal models, suggesting the potential for use to prevent and treat Alzheimer's disease.

Experimental approach: Here, 50 compounds, including isoflavone derivatives, were constructed and screened for the inhibitory effects on amyloid-β42 fibrilization and oligomerization using the high-throughput screening formats of thioflavin T assay and multimer detection system, respectively. The potential neuroprotective effect of t3-(4-hydroxyphenyl)-2H-chromen-7-ol (SPA1413), also known as dehydroequol, idronoxil or phenoxodiol, was evaluated in cells and in 5xFAD (B6SJL) transgenic mouse, a model of Alzheimer's disease.

Key results: SPA1413 had a potent inhibitory action on both amyloid-β fibrilization and oligomerization. In the cellular assay, SPA1413 prevented amyloid-β-induced cytotoxicity and reduced neuroinflammation. Remarkably, the oral administration of SPA1413 ameliorated cognitive impairment, decreased amyloid-β plaques and activated microglia in the brain of 5xFAD (B6SJL) transgenic mouse.

Conclusion and implications: Our results strongly support the repurposing of SPA1413, which has already received fast-track status from the US Food and Drug Administration (FDA) for cancer treatment, for the treatment of Alzheimer's disease due to its potent anti-amyloidogenic and anti-neuroinflammatory actions.

Keywords: Alzheimer's disease; drug discovery; isoflavone; neuroinflammation; oligomerization.

PubMed Disclaimer

References

REFERENCES

    1. Akiyama, H., Barger, S., Barnum, S., Bradt, B., Bauer, J., Cole, G. M., Cooper, N. R., Eikelenboom, P., Emmerling, M., Fiebich, B. L., Finch, C. E., Frautschy, S., Griffin, W. S., Hampel, H., Hull, M., Landreth, G., Lue, L., Mrak, R., Mackenzie, I. R., … Wyss-Coray, T. (2000). Inflammation and Alzheimer's disease. Neurobiology of Aging, 21(3), 383-421. https://doi.org/10.1016/s0197-4580(00)00124-x
    1. Alexander, S. P., Christopoulos, A., Davenport, A. P., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Davies, J. A., Abbracchio, M. P., Alexander, W., Al-hosaini, K., Bäck, M., Barnes, N. M., Bathgate, R., … Ye, R. D. (2021). The Concise Guide to PHARMACOLOGY 2021/22: G protein-coupled receptors. British Journal of Pharmacology, 178(S1), S27-S156. https://doi.org/10.1111/bph.15538
    1. Alexander, S. P. H., Roberts, R. E., Broughton, B. R. S., Sobey, C. G., George, C. H., Stanford, S. C., Cirino, G., Docherty, J. R., Giembycz, M. A., Hoyer, D., Insel, P. A., Izzo, A. A., Ji, Y., MacEwan, D. J., Mangum, J., Wonnacott, S., & Ahluwalia, A. (2018). Goals and practicalities of immunoblotting and immunohistochemistry: A guide for submission to the British Journal of Pharmacology. British Journal of Pharmacology, 175(3), 407-411. https://doi.org/10.1111/bph.14112
    1. An, S. S. A., Lee, B.-S., Yu, J. S., Lim, K., Kim, G. J., Lee, R., Kim, S., Kang, S., Park, Y. H., Wang, M. J., Yang, Y. S., Youn, Y. C., & Kim, S. (2017). Dynamic changes of oligomeric amyloid β levels in plasma induced by spiked synthetic Aβ42. Alzheimer's Research & Therapy, 9(1), 86-86. https://doi.org/10.1186/s13195-017-0310-6
    1. Arosio, P., Vendruscolo, M., Dobson, C. M., & Knowles, T. P. J. (2014). Chemical kinetics for drug discovery to combat protein aggregation diseases. Trends in Pharmacological Sciences, 35(3), 127-135. Retrieved from http://www.sciencedirect.com/science/article/pii/S0165614713002320. https://doi.org/10.1016/j.tips.2013.12.005

Publication types

LinkOut - more resources