Abstract

Amyloid-β (Aβ) has been closely implicated in the pathogenesis of cerebral amyloid angiopathy (CAA) and Alzheimer’s disease (AD), the major causes of dementia. Thus, Aβ could be a target for the treatment of these diseases, for which, currently, there are no established effective treatments. Taxifolin is a bioactive catechol-type flavonoid present in various plants, such as herbs, and it exhibits pleiotropic effects including anti-oxidant and anti-glycation activities. Recently, we have demonstrated that taxifolin inhibits Aβ fibril formation in vitro and have further shown that it improves cerebral blood flow, facilitating Aβ clearance in the brain and suppressing cognitive decline in a mouse model of CAA. These findings suggest the novel therapeutic potentials of taxifolin for CAA. Furthermore, recent extensive studies have reported several novel aspects of taxifolin supporting its potential as a therapeutic drug for AD and metabolic diseases with a high risk for dementia as well as for CAA. In this review, we have summarized the recent advances in taxifolin research based on in vitro, in vivo, and in silico approaches. Furthermore, we have discussed future research directions on the potential of taxifolin for use in novel therapeutic strategies for CAA, AD, and metabolic diseases with an increased risk for dementia.

Highlights

  • Cerebral amyloid angiopathy (CAA), pathologically characterized by the deposition of amyloid-β (Aβ) within small cerebral arteries, is a major cause of cerebrovascular diseases

  • Overproduction of Aβ or failure to eliminate it results in its accumulation; several investigations regarding sporadic Alzheimer’s disease (AD) and CAA have shown that the latter is critical [14,15], suggesting that promoting Aβ clearance would be a therapeutic approach for CAA [16]

  • Aβ distribution in CAA as well as vaccinated AD cases closely corresponds to the intramural periarterial drainage (IPAD) route, which is one of the major systems related to Aβ elimination [21]

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Summary

Introduction

Cerebral amyloid angiopathy (CAA), pathologically characterized by the deposition of amyloid-β (Aβ) within small cerebral arteries, is a major cause of cerebrovascular diseases. 40% of intracerebral hemorrhage (ICH) cases are associated with moderate or severe CAA in the UK [1]. There are no established treatments for CAA [2]. Despite great advances in ischemic stroke care, long-term prognosis of ICH remains a cause for concern [3]. We have recently reported that taxifolin, a catechol-type flavonoid with strong anti-oxidant and anti-glycation activities, inhibits Aβ aggregation, reducing cerebrovascular Aβ accumulation. This review mainly focuses on the potential of taxifolin as a novel treatment for CAA and other diseases

Cerebral Amyloid Angiopathy
Strategies to Tackle Cerebral Amyloid Angiopathy
Therapeutic Effects of Taxifolin on Cerebral Amyloid Angiopathy
Inhibitory Effects of Taxifolin on Amyloid-β42 Fibril Formation
Suppressive Effects of Taxifolin on Neuronal Amyloid-β Production
Potential Therapeutic Effects of Taxifolin on Alzheimer’s Disease
Effects of Taxifolin on Diabetes
Effects of Taxifolin on Diabetic Nephropathy
Findings
Effects of Taxifolin on Obesity
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