Title
A Peptide Based Pro-drug Disrupts Alzheimer’s Amyloid into Non-toxic Species and Reduces Aβ Induced Toxicity In Vitro
Author
Ashim Paul, Sourav Kumar, Sourav Kalita, Anup Kumar Ghosh, Amal Chandra Mondal, Bhubaneswar Mandal
Year
2017
Journal
International Journal of Peptide Research and Therapeutics
Abstract
Aggregation of Amyloid β (Aβ) in the interneuronal spaces is a major etiopathological factor for onset and progression of Alzheimer’s disease (AD). Since the mechanism of aggregation is not fully understood, control and modulation of the aggregation process is a challenging task. Although, several strategies were developed for the past few decades, yet there is no proper therapeutics available. Herein, we report a peptide based pro-drug, termed as a conformational Pro-Drug peptide (PDp), which disrupts existing Aβ fibrils, but does not produce toxic soluble oligomers, through a series of spontaneous chemical reactions resulting in in situ generation of β-sheet destabilizing factors. Furthermore, PDp reduces Aβ mediated toxicity examined on an in vitro model consisting of the human neuroblastoma SH-SY5Y cells. PDp also disrupts fibrils originated from AD affected human cerebrospinal fluid. These findings will help to understand the process of amyloidogenesis better and also indicate a novel approach for therapeutically important peptide design.
Instrument
J-1500
Keywords
Circular dichroism, Secondary structure, Aggregation, Biochemistry, Pharmaceutical