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

ACS Omega
Yujuan FanJianxiu Wang

Abstract

The aggregation or misfolding of amyloid-β (Aβ) is a major pathological hallmark of Alzheimer's disease (AD). The regulation of Aβ aggregation is thought to be an effective strategy for AD treatment. The capability of a water-soluble porphyrin, 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP), to inhibit Aβ aggregation and to lower Aβ-induced toxicity was demonstrated. As evidenced by surface plasmon resonance and circular dichroism, TMPyP can not only disrupt Aβ aggregation but also disassemble the preformed Aβ 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 Aβ 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 μM, respectively. As a member of porphyrin family, TMPyP is of rather low cytotoxicity, and the cytotoxicity of the Aβ aggregates was also relieved upon coincubation with TMPyP. The excellent performance of TMPyP thus makes it a potential drug candidate for AD therapy.

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Citations

Sep 10, 2019·Journal of Molecular Recognition : JMR·Svitlana CherniiVladyslava Kovalska
Oct 14, 2019·Journal of Pharmaceutical and Biomedical Analysis·Angela De SimoneVincenza Andrisano
Jul 25, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yaliang HuangJianxiu Wang

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Methods Mentioned

BETA
fluorescence assay
chips
circular dichroism
atomic force microscopy
AFM
chip
NMR

Software Mentioned

AmberTools14
PyRED
MolDesigner Platform

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