周林副教授和魏少華教授課題組在TALANTA發(fā)表研究論文
Design and synthesis of thymine modified phthalocyanine for A beta protofibrils photodegradation and A beta peptide aggregation inhibition
Zhan, QC (Zhan, Qichen)[ 1 ] ; Shi, XQ (Shi, Xianqing)[ 1 ] ; Wang, T (Wang, Ting)[ 1 ] ; Hu, JH (Hu, Jinhui)[ 1 ] ; Zhou, JH (Zhou, Jiahong)[ 1 ] ; Zhou, L (Zhou, Lin)[ 1 ] *（周林）; Wei, SH (Wei, Shaohua)[ 1 ]*（魏少華）
[ 1 ] Nanjing Normal Univ, Jiangsu Collaborat Innovat Ctr Biomed Funct Mat, Jiangsu Key Lab Biofunct Mat, Coll Chem & Mat Sci,Key Lab Appl Photochem, Nanjing 210023, Jiangsu, Peoples R China
TALANTA,201901,191,27-38
The formation and accumulation of toxic amyloid beta (A beta) protofibrils in brain is recognized as the pathological hallmark of alzheimer's disease (A beta). Recent research indicated that photodynamic therapy (PDT) has potential to treat A beta because reactive oxygen species (ROS) generated by photosensitizers (PS) could degrades All protofibrils. Al3+ and Fe3+ were found at markedly high levels on and around A beta protofibrils comparing with the normal part of brain. Based on this, a thymine modified Zn phthalocyanine (T-ZnPc), which can specific recognize and has strong affinity with Fe3+ and Al3+, was designed and synthesized. The recognize, affinity, A beta protofibrils degradation and neuro protection process were monitored via ultraviolet absorption spectrometry (UV), fluorescence emission spectrum, transmission electron microscopy (TEM), flow cytometer and thiazolyl blue tetrazolium bromide (MTT) assay. The results revealed that such affinity effect greatly increases the molar extinction coefficient (from 1.70 x 10(4) to 4.67 x 10(4) and 3.30 x 10(4) after forming Fe-T-ZnPc and Al-T-ZnPc) and activates PDT activity of T-ZnPc to generate abundant ROS to degrade A beta protofibrils (62% and 81% degradation by Al-T-ZnPc and Fe-T-ZnPc) and prevent its neurotoxicity based on the statistical differences analysis. Besides, T-ZnPc could inhibit new A beta protofibrils formation and the chelation effect could reduce the free Fe3+ and Al3+ concentration in brain, which could be also helpful for AD treatment.
文章鏈接：
https://www.sciencedirect.com/science/article/pii/S0039914018308488?via%3Dihub
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