Aβ dissociation by pectolinarin may counteract against Aβ-induced synaptic dysfunction and memory impairment

Abstract

Alzheimer's disease (AD) is a degenerative brain disorder characterised by various neurological symptoms, including memory impairment and mood disorders, associated with the abnormal accumulation of amyloid b(A beta) and tau proteins in the brain. There is still no definitive treatment available for AD, and the A beta antibody drugs, which are expected to be approved by the FDA, have many limitations. Therefore, there is an urgent need to develop low-molecular-weight therapeutic agents for the management of AD. In this study, we investigated whether pectolinarin, a flavonoid, regulates A beta aggregation and A beta-induced toxicity. Pectolinarin demonstrated concentration-dependent inhibition of A beta aggregation and had the ability to break down pre-formed A beta aggregates, thereby reducing their neurotoxicity. Furthermore, pectolinarin suppressed A beta aggregates-induced reduction in long-term potentiation (LTP) in the hippocampus. Oral administration of pectolinarin in experimental animals inhibited memory impairment and LTP deficits induced by A beta injection in the hippocampus. These results indicate that pectolinarin may reduce toxic A beta species and A beta-induced memory impairments and synaptic dysfunction.