Inhibition of Amyloid-β Aggregation by p-Terphenyls from the Mushroom Polyozellus multiplex and Their Neuroprotective Effects

Abstract

The main pathogenesis of Alzheimer's disease (AD) is related to the accumulation of amyloid-b (Ab) peptides in the brain that leads to neuronal cell death. In this study, we identified compounds in a methanol extract of the fruiting body of Polyozellus multiplex that inhibited Ab aggregation and are neuroprotective.Seven compounds against Ab40 aggregation were obtained through bioactivityguided fractionation of the extract, including polyozellin (1), kynapcin-12 (2), NSC617425 (3), cycloleucomelone (4), Bl-V (5), succinic acid (6), and protocatechuic acid (7). Compounds 1-5 inhibited Ab40 aggregation in a dosedependent manner. Moreover, compounds 2-5 protected SH-SY5Y cells from Ab toxicity. Therefore, these compounds are potential agents in AD treatment.Dementia is a neurodegenerative disease caused by acquired organic brain damage. The disease is characterized by a persistent loss of cognitive function that interferes with daily and social life. Alzheimer's disease (AD) is the most frequent cause of dementia 1 ; its pathological features include neuronal loss (mainly in the cerebral cortex), neurofibrillary tangles, and the occurrence of senile plaques in the brain parenchyma.Senile plaques are composed of amyloid-b (Ab) peptides. 2 Normally, Ab peptides are degraded and/or eliminated. However, excessive accumulation of Ab forms senile plaques, eventually leading to AD, which is known as the amyloid cascade hypothesis. 3 Ab is a partial fragment of amyloid precursor protein (APP), which is produced by the cleavage of b-secretase 1 (BACE1) and γ-secretase and is subsequently secreted into the extracellular milieu. [4][5][6] Ab undergoes degradation by various extracellular pathways. Therefore, 2025