RESUMO
Alzheimer's disease (AD) is a progressive neurodegenerative brain disease and is the most common cause of dementia in the elderly. The main hallmark of AD is the deposition of insoluble amyloid (Aß) outside the neuron, leading to amyloid plaques and neurofibrillary tangles in the brain. Deuterohemin-Ala-His-Thr-Val-Glu-Lys (DhHP-6), a novel porphyrin-peptide, has both microperoxidase activity and cell permeability. In the present study, DhHP-6 efficiently inhibited the aggregation of Aß and reduced the ß-sheet percentage of Aß from 89.1% to 78.3%. DhHP-6 has a stronger affinity (KDâ¯=â¯100⯱â¯12⯵M) for binding with Aß at Phe4, Arg5, Val18, Glu11 and Glu22. In addition, DhHP-6 (100⯵M) significantly prolonged lifespan, alleviated paralysis and reduced Aß plaque formation in the Aß1-42 transgenic Caenorhabditis elegans CL4176 model of AD. Our results demonstrate that DhHP-6 is a potential drug candidate that efficiently protects a transgenic C. elegans model of Alzheimer's disease by inhibiting Aß aggregation.