TMPyP Inhibits Amyloid-β Aggregation and Alleviates Amyloid-Induced Cytotoxicity

The aggregation or misfolding of amyloid-beta(A beta) is a major pathological hallmark of Alzheimer's disease (AD). The regulation of A beta aggregation is thought to be an effective strategy for AD treatment. The capability of a watersoluble porphyrin, 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP), to inhibit A beta aggregation and to lower A beta-induced toxicity was demonstrated. As evidenced by surface plasmon resonance and circular dichroism, TMPyP can not only disrupt A beta aggregation but also disassemble the preformed A beta aggregates. The atomic force microscopy imaging proves that TMPyP inhibits the formation of both oligomers and fibrils. Molecular dynamic simulations provide an insight into the interaction between TMPyP and A beta at the molecular level. The half-maximal inhibitory concentrations of TMPyP acting on the oligomers and fibrils were determined to be 0.6 and 0.43 mu M, respectively. As a member of porphyrin family, TMPyP is of rather low cytotoxicity, and the cytotoxicity of the A beta aggregates was also relieved upon coincubation with TMPyP. The excellent performance of TMPyP thus makes it a potential drug candidate for AD therapy.