C-Terminal Fragment, Aβ32–37, Analogues Protect Against Aβ Aggregation-Induced Toxicity

详细信息    查看全文

• 作者：Sunil Bansal ; Indresh Kumar Maurya ; Nitin Yadav ; Chaitanya Kumar Thota ; Vinod Kumar ; Kulbhushan Tikoo ; Virander Singh Chauhan ; Rahul Jain
• 刊名：ACS Chemical Neuroscience
• 出版年：2016
• 出版时间：May 18, 2016
• 年：2016
• 卷：7
• 期：5
• 页码：615-623
• 全文大小：460K
• 年卷期：0
• ISSN：1948-7193

文摘

Amyloid-β aggregation is a major etiological phenomenon in Alzheimer’s disease. Herein, we report peptide-based inhibitors that diminish the amyloid load by obviating Aβ aggregation. Taking the hexapeptide fragment, Aβ_32–37, as lead, more than 40 new peptides were synthesized. Upon evaluation of the newly synthesized hexapeptides as inhibitors of Aβ toxicity by the MTT-based cell viability assay, a number of peptides exhibited significant Aβ aggregation inhibitory activity at sub-micromolar concentration range. A hexapeptide (1) showed complete mitigation of Aβ toxicity in the cell culture assay at 2 μM. In the ThT fluorescence assay, upon incubation of Aβ with this peptide, we observed no increase in the ThT fluorescence relative to control. The secondary structure estimation by circular dichroism spectroscopy and morphological examination by transmission electron microscopy further confirmed the results.