Conformational-specific self-assembled peptides as dual-mode, multi-target inhibitors and detectors for different amyloid proteins

Abstract

Prevention and detection of misfolded amyloid proteins and their β-structure-rich aggregates are the two promising but differ-ent (pre)clinical strategies to treat and diagnose neurodegenerative diseases including Alzheimer’s diseases (AD) and...

Design of aggregation-induced emission-active fluorogen-based nanoparticles for imaging and scavenging Alzheimer's β-amyloid by photo-oxygenation

“…As reported previously, diverse Ab scavengers, including small molecules, 12,13 proteins, 14 nanomaterials, 15,16 and peptides, 17,18 have been designed to modulate the on-pathway fibrillization. When compared with others, the scavengers based on nanomaterials display outstanding advantages, such as easy functionalization, desirable biodegradability, and high biocompatibility.…”

Atrial Natriuretic Peptide Associated with Cardiovascular Diseases Inhibits Amyloid-β Aggregation via Cross-Seeding

“…The worm results showed that ANP significantly inhibited AD-like symptoms of worm paralysis, suppressed Aβ deposits in the head region of the worms, and diminished ROS production caused by oxidative stress. From an amyloid inhibitor viewpoint in Figure , most of the peptide-based Aβ inhibitors , comprise short sequences with ≤10 residues, which exhibit some intrinsic disadvantages, including (i) limited inhibition efficiency (equimolar inhibitors only lead to <30% inhibition of Aβ aggregation), (ii) high concentrations (inhibitor: Aβ > 6:1), (iii) poor cell protection (∼20–60% of cell viability), or (iv) low binding affinity ( K D = 9–156 μM). , For comparison, peptide inhibitors with residues >10 are more efficient at inhibiting Aβ aggregation and toxicity, presumably due to their high enzymatic proteolysis resistance, high structural stability, and multiple reactive sites. For instance, equimolar antimicrobial peptides of defensins can inhibit 100% Aβ aggregation and thus rescue 35% of neuron cells, while a very small amount of SEVI (1 μM) can completely inhibit Aβ aggregation (20 μM) and increase cell viability by 40% .…”