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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
Abstract:
Background and purpose: Isoflavone derivatives recently presented neuroprotective effects against neurological disorders. For instance, genistein attenuated the neuroinflammation and Aβ accumulation in Alzheimer's disease, suggesting the potential for the prevention and treatment of Alzheimer's disease.
Experimental approach: Here, the fifty compounds including isoflavone derivatives were constructed and screened for the inhibition effects in Aβ42 fibrilization and oligomerization by the high-throughput screening formats of thioflavin T assay and multimer detection system, respectively. The potential neuroprotective effect of the 3-(4-hydroxyphenyl)-2H-chromen-7-ol (SPA1413) compound was evaluated in cells and a 5xFAD (B6SJL) transgenic mouse, Alzheimer's disease animal model.
Key results: SPA1413, also known as dehydroequol, phenoxodiol, and idronoxil, revealed potent both Aβ fibrilization and oligomerization inhibition. In the cellular system, SPA1413 prevented the Aβ-induced cytotoxicity and reduced the neuroinflammation. Remarkably, the oral administration of SPA1413 ameliorated the cognitive impairment and decreased Aβ plaques and the activated microglia in the brain of 5xFAD (B6SJL) transgenic mouse Alzheimer's disease model.
Conclusion and implications: Our results strongly support the repurposing potential of SPA1413, which received a fast track status from the US-FDA for cancer treatment, targeting the anti-amyloidogenic and anti-neuroinflammatory activities for Alzheimer's disease.
Experimental approach: Here, the fifty compounds including isoflavone derivatives were constructed and screened for the inhibition effects in Aβ42 fibrilization and oligomerization by the high-throughput screening formats of thioflavin T assay and multimer detection system, respectively. The potential neuroprotective effect of the 3-(4-hydroxyphenyl)-2H-chromen-7-ol (SPA1413) compound was evaluated in cells and a 5xFAD (B6SJL) transgenic mouse, Alzheimer's disease animal model.
Key results: SPA1413, also known as dehydroequol, phenoxodiol, and idronoxil, revealed potent both Aβ fibrilization and oligomerization inhibition. In the cellular system, SPA1413 prevented the Aβ-induced cytotoxicity and reduced the neuroinflammation. Remarkably, the oral administration of SPA1413 ameliorated the cognitive impairment and decreased Aβ plaques and the activated microglia in the brain of 5xFAD (B6SJL) transgenic mouse Alzheimer's disease model.
Conclusion and implications: Our results strongly support the repurposing potential of SPA1413, which received a fast track status from the US-FDA for cancer treatment, targeting the anti-amyloidogenic and anti-neuroinflammatory activities for Alzheimer's disease.
