2 research outputs found
Synthesis and Evaluation of Amyloid β Derived and Amyloid β Independent Enhancers of the Peroxidase-like Activity of Heme
Labile
heme has been suggested to have an impact in several severe
diseases. In the context of Alzheimer’s disease (AD), however,
decreased levels of free heme have been reported. Therefore, we were
looking for an assay system that can be used for heme concentration
determination. From a biochemical point of view the peroxidase activity
of the Aβ-heme complex seemed quite attractive to pursue this
goal. As a consequence, a peptide that is able to increase the readout
even in the case of a low heme concentration is favorable. The examination
of Aβ- and non-Aβ-derived peptides in complex with heme
revealed that the peroxidase-like activity significantly depends on
the peptide sequence and length. A 23mer His-based peptide derived
from human fatty acyl-CoA reductase 1 in complex with heme exhibited
a significantly higher peroxidase activity than Aβ(40)-heme.
Structural modeling of both complexes demonstrated that heme binding
via a histidine can be supported by hydrogen bond interactions of
a basic residue near the propionate carboxyl function of protoporphyrin
IX. Furthermore, the interplay of Aβ-heme and the lipoprotein
LDL as a potential physiological effector of Aβ was examined
Structure and Biomedical Applications of Amyloid Oligomer Nanoparticles
Amyloid oligomers are nonfibrillar polypeptide aggregates linked to diseases, such as Alzheimer’s and Parkinson’s. Here we show that these aggregates possess a compact, quasi-crystalline architecture that presents significant nanoscale regularity. The amyloid oligomers are dynamic assemblies and are able to release their individual subunits. The small oligomeric size and spheroid shape confer diffusible characteristics, electrophoretic mobility, and the ability to enter hydrated gel matrices or cells. We finally showed that the amyloid oligomers can be labeled with both fluorescence agents and iron oxide nanoparticles and can target macrophage cells. Oligomer amyloids may provide a new biological nanomaterial for improved targeting, drug release, and medical imaging