A deuterohemin peptide protects a transgenic Caenorhabditis elegans model of Alzheimer's disease by inhibiting Aβ aggregation.

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 (Aβ) 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 Aβ and reduced the β-sheet percentage of Aβ from 89.1% to 78.3%. DhHP-6 has a stronger affinity (K = 100 ± 12 μM) for binding with Aβ at Phe, Arg, Val, Glu and Glu. In addition, DhHP-6 (100 μM) significantly prolonged lifespan, alleviated paralysis and reduced Aβ plaque formation in the Aβ 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 Aβ aggregation.