2 research outputs found
Hematoxylin Inhibits Amyloid β‑Protein Fibrillation and Alleviates Amyloid-Induced Cytotoxicity
Accumulation and
aggregation of amyloid β-protein (Aβ)
play an important role in the pathogenesis of Alzheimer’s disease.
There has been increased interest in finding new anti-amyloidogenic
compounds to inhibit Aβ aggregation. Herein, thioflavin T fluorescent
assay and transmission electron microscopy results showed that hematoxylin,
a natural organic molecule extracted from <i>Caesalpinia sappan</i>, was a powerful inhibitor of Aβ42 fibrillogenesis. Circular
dichroism studies revealed hematoxylin reduced the β-sheet content
of Aβ42 and made it assemble into antiparallel arrangement,
which induced Aβ42 to form off-pathway aggregates. As a result,
hematoxylin greatly alleviated Aβ42-induced cytotoxicity. Molecular
dynamics simulations revealed the detailed interactions between hematoxylin
and Aβ42. Four binding sites of hematoxylin on Aβ42 hexamer
were identified, including the N-terminal region, S8GY10 region, turn
region, and C-terminal region. Notably, abundant hydroxyl groups made
hematoxylin prefer to interact with Aβ42 via hydrogen bonds.
This also contributed to the formation of π–π stacking
and hydrophobic interactions. Taken together, the research proved
that hematoxylin was a potential agent against Aβ fibrillogenesis
and cytotoxicity
Assembly Pathway Selection of Designer Self-Assembling Peptide and Fabrication of Hierarchical Scaffolds for Neural Regeneration
The
self-assembling peptide (SAP) RADA 16-I has been modified with
various functional motifs to improve its performances in biomedical
applications. Nevertheless, the assembly mechanisms of designer functional
RADA 16-I SAPs (F-SAPs) have not been clearly illustrated. The main
problem is the difficulty in preparing a completely molecular aqueous
solution of F-SAP. In the current study, we demonstrated that different
procedures for preparing the F-SAP solution could result in the formation
of different conformations and consequently micro/macroscopic morphologies.
F-SAP was molecularly dissolved in an appropriate solvent, such as
hexafluoroisopropanol (HFIP), as evidenced by random coil conformation
characterized by circular dichroism spectroscopy and morphologies
under transmission electron microscopy. The monomers were induced
into monolayers when the F-SAP solution in HFIP was adsorbed on mica
as observed by atomic force microscopy. However, nanoscaled filaments
containing β-sheets dominated in the F-SAP aqueous solution,
in which case water acted as a poor solvent of F-SAP. Furthermore,
the results of molecular dynamics simulation implicated that water
facilitated F-SAP aggregation, whereas HFIP inhibited it. The β-sheet
assemblies formed in water exhibited a high kinetic stability and
did not disassemble rapidly after the addition of HFIP. Our study
indicated that selecting the right assembly pathway of F-SAP required
for targeted functions, for example, delivery of hydrophobic drugs
in aqueous conditions, could be achieved by optimizing the preparation
protocol in addition to molecular design. Moreover, hierarchical scaffolds
mimicking the natural extracellular matrix could be fabricated by
the direct electrospinning of F-SAP molecular solution in HFIP and
biodegradable polymer for applications in neural regeneration by promoting
neural differentiation, neurite outgrowth, and synapse formation