Extending Lifespan of Alzheimer's Mode Nematode CL4176 Using a Novel Bifunctional Peptide with Inhibition of β-Amyloid Aggregation and Anti-oxidation

• 来源期刊: 高等学校化学研究（英文版）
• 年，卷（期）: 2019,（2）
• 页码范围: 245-250
• 页数: 6页
• 语种: 英文
• DOI: 10.1007/S40242-019-8299-y

摘要

Alzheimer's disease(AD) is a neurodegenerative disorder characterized by the deposition of β-amyloid peptide(Aβ) in the brain tissues,and an imbalance in the oxidant-antioxidant system.Compounds with antioxidant activity and the ability to inhibit Aβ aggregation therefore potentially treat AD.In this study,we designed an iron-porphyrin containing bifunctional peptide(BP,Deuterohemin-AlaHisThrValGluLysLeuProPhePheAsp) based on natural microperoxidase-11(MP-11) and typical β-sheet breaker LPFFD(iAβ5p).This BP substantially reduced the aggregation of Aβ and caused oligomer disassembly,by binding Aβ with affinity constant of 9.07 μmol/L.Furthermore,it showed a neuroprotective effect on Aβ25-35 induced toxicity in SH-SY5Y cells,and significantly alleviated Aβ-induced paralysis and extended lifespan in Aβ1-42 transgenic C.elegans(CL4176).It also showed a potent peroxidase activity of 20.8 U/mg,and scavenged free radicals both in vitro and in vivo.In addition,BP up-regulated the levels of hsp16.2,hsp16.41,and hsp12.6 mRNAs to 183.26％,160.16％,and 162.64％ respectively,and down-regulated that ofhsp70 to 36.76％ in C.elegans.Taken together,the synthetic BP inhibited Aβ aggregation and showed antioxidant activity,indicating the therapeutic potential of novel peptide drugs against AD.