Post on 13-Aug-2020
Amyloid β‐sheet mimic that antagonize protein aggregation and reduce amyloid toxicityPin‐Nan Cheng, Cong Liu, Minglei Zhao, David Eisenberg, and James Nowick
Presented by: Seth RitterNovember 13th, 2013
Amyloid Protein Aggregation Diseases
• Wide variety of diseases– Alzheimer’s, Parkinson’s, type II diabetes, etc
• Great variety of β‐sheet‐rich structures in associated proteins
• Energetically driven, aggregation process to form oligomers and fibres which are then toxic
Amyloid β‐Sheet Mimics (ABSMs)
ABSMs
Structure of ABSM 1r (Aβ30‐36)
Inhibiting Fibril Formation
• ABSMs designed to homotipically interact with varying sections of target proteins
• ABSMs conformationally bind best to β‐sheet structure (specific step in fibril formation process)
Inhibiting Fibril Formation
Hβ2M Aggregation Inhibition
Aβ42 Aggregation Inhibition
Aβ40 Aggregation Inhibition
hαSyn1‐100 Aggregation Inhibition
Lag‐Time Comparisons
EM+A
BSM
Control
Aβ40 Aβ42 Hβ2M hαSyn1‐100
Cell Survival
Cross Reactions of Aβ with ABSMs
Other Portions of Aβ40
Conclusion
• ABSMs provide platform to display heptapeptide β‐strands– Can be tailored to inhibit different amyloid proteins
– Can help elucidate fibrilization mechanisms
• Suggested potential therapeutic applications to detoxify amyloid aggregates