Copper chelating cyclic peptidomimetic inhibits Aβ fibrillogenesis

Abstract

Misfolding of amyloid- peptide (A) and its subsequent aggregation into toxic oligomers is one of the leading causes of Alzheimer's disease (AD). As a therapeutic approach, cyclic peptides have been...

Succinate and inosine coordinate innate immune response to bacterial infection

“…The results indicate that inosine dramatically decreased the affinity of succinate for PHD (7.65 μM vs. 33.7 μM, respectively) while succinate also decreased the affinity of inosine for PHD (15.5 μM vs. 43.8 μM, respectively) ( Fig 4B ). Moreover, isothermal titration calorimetry (ITC) was adopted to confirm this conclusion as previously described [ 35 ]. During titration, constant volume of metabolites (succinate or inosine or both) were added to PHD protein solutions.…”

Harnessing the Therapeutic Potential of Peptides for Synergistic Treatment of Alzheimer’s Disease by Targeting Aβ Aggregation, Metal-Mediated Aβ Aggregation, Cholinesterase, Tau Degradation, and Oxidative Stress

“…Several MTD peptides against AD reported in this review can themselves act as guiding chemotypes for the development of potent therapeutics against AD. 46 tested in cellular model (SH-SY5Y cells) LA-GPE 47 tested in cellular model (SH-SY5Y cells) GS(HQ)H 48 tested in cellular model (SH-SY5Y cells) ZW1 51 tested in transgenic mouse model GGH 52 tested in cellular model (PC12 cells) P6 53 tested in cellular model (PC12 cells) GR 54,55 tested in cellular model (PC12 cells) and rat model GSH-LD 56 tested in cellular model (U937 cell lines) LK7-HH 58 tested in cellular model (PC12 cells) Car-LK7 59 tested in cellular model (SH-SY5Y cells) RK10 61 tested in cellular model (SH-SY5Y cells) rk10 62 tested in cellular model (SH-SY5Y cells) Glupep 66 tested in cellular model (PC12 cells) MPLT3, MPGLT 67 tested in cellular model (SH-SY5Y cells) PA 19 fCP 68 tested in cellular model (N2a cells) Semax 69 tested in cellular model (SH-SY5Y cells) DS2 70 tested in cellular model (SH-SY5Y cells) WRR, ERW 71 tested in cellular model (SH-SY5Y cells) TH006 74 tested in rat model AI 75 tested in cellular model (PC12 cells) LE6 76 tested in cellular model (PC12 cells) SLKP 77 tested in cellular model (PC12 cells) NVR 78 tested in cellular model (PC12 cells) W3 79 tested in brine shrimp RA-1 80 tested in cellular model (PC12 cells) LME-tet 85 tested in cellular model (N2a cells)…”

“…In 2022, Mandal and co-workers reported a cyclic peptidomimetic (PA 19 fCP) that could inhibit Aβ 40 aggregation and metal-induced Aβ 40 aggregation (Figure 8). 68 The PA 19 fCP was a combination of the metal chelator picolinic acid (PA) and a cyclic peptide, [Lys-Leu-Val-(D-Phe)-Phe-Ala-Gln]. The ThT fluorescence assay and TEM revealed that PA 19 fCP, 19 fCP (cyclic peptide without PA), and 19 fLP (linear analog) showed 85.56%, 73.72%, and 27.12% inhibition, respectively, of Aβ 40 aggregation at a 1:2 molar ratio of Aβ 40 /ligand (Aβ 40 = 40 μM).…”

Editorial Commentary: Copper Homeostasis in Neurodegenerative Diseases

“…Research on coproptosis and neurodegenerative diseases contributes to a deeper understanding of the pathogenic mechanisms of these diseases and provides clues for the development of new therapeutic strategies. For instance, regulating copper metabolism and chelating copper ions could be potential therapeutic approaches [23] . Furthermore, studying the interaction between copper death and other forms of cell death, such as ferroptosis, both induced by the accumulation of metal ions, reveals a close correlation in occurrence, cellular metabolism, signaling pathways, and drug resistance [24,25] .…”