Abstract
The Aβ peptide assembles into a variety of distinct types of structures in vitro and in the brain which have different biological consequences. Differential effects of inhibitory small molecules suggest that a sequential monomer – oligomer – fibril mechanism is overly simplistic and that soluble toxic oligomers and fibrils can be formed in common or separate pathways depending on the local environment. As a result, the effects of inhibitors are often assay-dependent because multiple pathways are operating. This review discusses strategies for teasing apart the intricate protein–protein interactions that result in Aβ assembly.
Abbreviations | ||
ADDLs | = | Alzheimer Disease Diffusible Ligands; |
AFM | = | atomic force microscopy; |
βAPP | = | amyloid precursor protein; |
ELISA | = | enzyme-linked immunosorbent assay; |
EM | = | electron microscopy; |
GAG | = | glycosaminoglycan; |
IAPP | = | islet amyloid polypeptide; |
PS1 | = | presenilin-1; |
SAR | = | structure activity relationship |
Abbreviations | ||
ADDLs | = | Alzheimer Disease Diffusible Ligands; |
AFM | = | atomic force microscopy; |
βAPP | = | amyloid precursor protein; |
ELISA | = | enzyme-linked immunosorbent assay; |
EM | = | electron microscopy; |
GAG | = | glycosaminoglycan; |
IAPP | = | islet amyloid polypeptide; |
PS1 | = | presenilin-1; |
SAR | = | structure activity relationship |