2 research outputs found
Inside out <i>Porphyridium cruentum</i>: Beyond the Conventional Biorefinery Concept
Here, an unprecedented
biorefinery approach has been designed to
recover high-added value bioproducts starting from the culture ofPorphyridium cruentum. This unicellular marine red
alga can secrete and accumulate high-value compounds that can find
applications in a wide variety of industrial fields. 300 ± 67
mg/L of exopolysaccharides were obtained from cell culture medium;
phycoerythrin was efficiently extracted (40% of total extract) and
isolated by single chromatography, with a purity grade that allowed
the crystal structure determination at 1.60 Å; a twofold increase
in β-carotene yield was obtained from the residual biomass;
the final residual biomass was found to be enriched in saturated fatty
acids. Thus, for the first time, a complete exploitation ofP. cruentumculture was set up
Inhibition of Aβ Amyloid Growth and Toxicity by Silybins: The Crucial Role of Stereochemistry
The
self-assembling of the amyloid β (Aβ) peptide into neurotoxic
aggregates is considered a central event in the pathogenesis of Alzheimer’s
disease (AD). Based on the “amyloid hypothesis”, many
efforts have been devoted to designing molecules able to halt disease
progression by inhibiting Aβ self-assembly. Here, we combine
biophysical (ThT assays, TEM and AFM imaging), biochemical (WB and
ESI-MS), and computational (all-atom molecular dynamics) techniques
to investigate the capacity of four optically pure components of the
natural product silymarin (silybin A, silybin B, 2,3-dehydrosilybin
A, 2,3-dehydrosilybin B) to inhibit Aβ aggregation. Despite
TEM analysis demonstrated that all the four investigated flavonoids
prevent the formation of mature fibrils, ThT assays, WB and AFM investigations
showed that only silybin B was able to halt the growth of small-sized
protofibrils thus promoting the formation of large, amorphous aggregates.
Molecular dynamics (MD) simulations indicated that silybin B interacts
mainly with the C-terminal hydrophobic segment <sup>35</sup>MVGGVV<sup>40</sup> of Aβ40. Consequently to silybin B binding, the peptide
conformation remains predominantly unstructured along all the simulations.
By contrast, silybin A interacts preferentially with the segments <sup>17</sup>LVFF<sup>20</sup> and <sup>27</sup>NKGAII<sup>32</sup> of
Aβ40 which shows a high tendency to form bend, turn, and β-sheet
conformation in and around these two domains. Both 2,3-dehydrosilybin
enantiomers bind preferentially the segment <sup>17</sup>LVFF<sup>20</sup> but lead to the formation of different small-sized, ThT-positive
Aβ aggregates. Finally, in vivo studies in a transgenic Caenorhabditis elegans strain expressing human Aβ
indicated that silybin B is the most effective of the four compounds
in counteracting Aβ proteotoxicity. This study underscores the
pivotal role of stereochemistry in determining the neuroprotective
potential of silybins and points to silybin B as a promising lead
compound for further development in anti-AD therapeutics