Hyperforin prevents |[beta]|-amyloid neurotoxicity and spatial memory impairments by disaggregation of Alzheimer's amyloid-|[beta]|-deposits

摘要

The major protein constituent of amyloid deposits in Alzheimer's disease (AD) is the amyloid -peptide (A). In the present work, we have determined the effect of hyperforin an acylphloroglucinol compound isolated from Hypericum perforatum (St John's Wort), on A-induced spatial memory impairments and on A neurotoxicity. We report here that hyperforin: (1) decreases amyloid deposit formation in rats injected with amyloid fibrils in the hippocampus; (2) decreases the neuropathological changes and behavioral impairments in a rat model of amyloidosis; (3) prevents A-induced neurotoxicity in hippocampal neurons both from amyloid fibrils and A oligomers, avoiding the increase in reactive oxidative species associated with amyloid toxicity. Both effects could be explained by the capacity of hyperforin to disaggregate amyloid deposits in a dose and time-dependent manner and to decrease A aggregation and amyloid formation. Altogether these evidences suggest that hyperforin may be useful to decrease amyloid burden and toxicity in AD patients, and may be a putative therapeutic agent to fight the disease.