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[D. Medicine/Translational Research] D-13
The potential anti-amyloidogenic candidate. SPA1413, for
Alzheimer`s disease
young kyo Kim¹*, Shinwoo Kang ¹, Hyewon Cho¹, Raok Jeon ¹*, Keun-A Chang¹*
¹Department of Health Sciences and Technology, Gachon university, Inchon 155, Gaetbeol-ro, Yeonsu-gu, Incheon,
Republic of Korea, Korea
Alzheimer’s disease (AD), the most common cause of neurodegenerative disorder, is characterized by the deposition
of amyloid-beta (Aβ) and neurofibrillary tangles. 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. In this study, the fifty compounds including isoflavone derivatives were constructed and
evaluated for their inhibitory effects on Aβ oligomerization and fibrilization. Among the fifty compounds, SPA1413
was finally selected for anti-Aβ aggregation. Remarkably, the oral administration of SPA1413 ameliorated cognitive
impairment, decreased amyloid-β plaques, and activated microglia in the brain of 5xFAD (B6SJL) transgenic mouse.
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.
