Natural phenolic compounds as therapeutic and preventive agents for cerebral amyloidosis

Abstract

Epidemiological studies have suggested that diets rich in phenolic compounds may have preventive effects on the development of dementia or Alzheimer’s disease (AD). We investigated the effects of natural phenolic compounds, such as myricetin (Myr), rosmarinic acid (RA), ferulic acid (FA), curcumin (Cur) and nordihydroguaiaretic acid (NDGA) on the aggregation of amyloid “-protein (A“), using in vitro and in vivo models of cerebral A“ amyloidosis. The in vitro studies revealed that these phenolic compounds efficiently inhibit oligomerization as well as fibril formation of A“ through differential binding, whilst reducing A“ oligomer-induced synaptic and neuronal toxicity. Furthermore, a transgenic mouse model fed orally with such phenolic compounds showed significant reduction of soluble A“ oligomers as well as of insoluble A“ deposition in the brain. These data, together with an updated review of the literature, indicate that natural phenolic compounds have anti-amyloidogenic effects on A“ in addition to well-known anti-oxidative and anti-inflammatory effects, hence suggesting their potential as therapeutic and/or preventive agents for cerebral A“ amyloidosis, including AD and cerebral amyloid angiopathy (CAA). Well-designed clinical trials or preventive interventions with natural phenolic compounds are necessary to establish their efficacy as disease-modifying agents.