Amyloid β and free heme：bloody new insights into the pathogenesis of Alzheimer＇s disease

The cerebral formation of Amyloid β（Aβ） is a critical pathological feature of Alzheimer＇s disease（AD）.An accumulation of this peptide as senile plaques（SP） was already reported by Alois Alzheimer,the discoverer of the disease.Yet the exact contribution of Aβ to AD development remains elusive.Moreover,while extensive cerebral Aβ formation leads to fibril formation in many species,AD-like symptoms apparently depend on the highly conserved N-terminal residues R5,Y10 and H13.The amino acids were also shown to lead to the formation of Aβ-heme complexes,which exhibit peroxidase activity in the presence of H_2O_2.Taking together these observations we propose that the formation and enzymatic activity of the named complexes may represent an essential aspect of AD pathology.Furthermore,Aβ is also known to lead to cerebral micro-vessel destruction（CAA） as well as to hemolytic events.Thus we suggest that the Aβ-derived cerebral accumulation of blood-derived free heme represents a likely precondition for the subsequent formation of Aβ-heme complexes.

The Interaction(s) between Calf-Skin Hyaluronic Acid (Hyaluronan) and Dermal Type I Calf-Skin Collagen under 254 nm UV Radiation: Ability of Hyaluronan to Alter Qualitative and Quantitative Dimerization of Collagen Tyrosine Residues

The extracellular matrix (ECM) is the non-cellular component present within all tissues and organs, providing not only essential physical scaffolding for the cellular constituents and initiating crucial biochemical and biomechanical cues, required for tissue morphogenesis, differentiation and homeostasis. Roughly divided into two groups, these are 1) the main fibrous ECM proteins: collagens, elastins, fibronectins and laminins. 2) Classification of proteoglycans (PGs) is based on their location and binding. Although many different molecular interactions are possible, they depend on the cells’ condition (i.e. “Normal”, Aged, Wounded/Fibrotic, and cancerous). There is little or no data that addresses the influence of the surrounding ECM on dityrosine formation. As a simpler model, we have replaced total PG with hyaluronan (HA) and have used purified calf-skin collagen tyrosine, which forms dityrosine (A2) under 254 nm UV in buffered solution and (near) physiological temperatures. Our results reveal a complicated temperature dependence involving factors relating to collagen HA structure, and collagen’s photochemical activation parameters.

Quick photofabrication of functional nanospheres from de novo designed peptides for NIR fluorescence and MR imaging

Combining the noncovalent and covalent interactions,a series of peptide amphiphiles were designed de novo and synthesized to architect functional assemblies by means of photochemistry.The strand of peptide sequence was structurally capped with photoactive tyrosine-tyrosine(YY)motifs at both termini,and the spacing was filled by alternating of hydrophilic D(L-aspartate)and hydrophobic X(ε-aminocaproic acid)structure.Upon visible-light irradiation,these de novo designed peptides underwent rapid photocrosslinking within merely 10 min.Interestingly,the modulation of alternating D-X pairs in occupying spacer would adjust molecular amphiphilicity,regulate charge distribution,and control particle size and loading capacity of peptide nanospheres(PNS)in aqueous media.With entirely peptide-based matrix,this PNS system could host cationic indicators of fluorescent rhodamine and magnetic GdIII for exemplar near infrared(NIR)fluorescence and magnetic resonance(MR)imaging,which paves a pathway to biomaterial and biomedical applications using de novo designed peptides.