Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-12346-8
Keywords
-
Categories
Funding
- NIH [R01DK071801, R56DK071801, RF1AG052324]
- NSF [CHE-1710140]
- National Institutes of Health-General Medical Sciences F31 National Research Service Award [1F31GM126870-01A1]
- American Society for Mass Spectrometry (2019)
- Wisconsin Alumni Research Foundation
- University of Wisconsin-Madison School of Pharmacy
Ask authors/readers for more resources
Despite extensive efforts on probing the mechanism of Alzheimer's disease (AD) and enormous investments into AD drug development, the lack of effective disease-modifying therapeutics and the complexity of the AD pathogenesis process suggest a great need for further insights into alternative AD drug targets. Herein, we focus on the chiral effects of truncated amyloid beta (A beta) and offer further structural and molecular evidence for epitope region-specific, chirality-regulated A beta fragment self-assembly and its potential impact on receptor-recognition. A multidimensional ion mobility-mass spectrometry (IM-MS) analytical platform and in-solution kinetics analysis reveal the comprehensive structural and molecular basis for differential A beta fragment chiral chemistry, including the differential and cooperative roles of chiral A beta N-terminal and C-terminal fragments in receptor recognition. Our method is applicable to many other systems and the results may shed light on the potential development of novel AD therapeutic strategies based on targeting the D-isomerized A beta, rather than natural L-A beta.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available