Modulating the aggregation of amyloid proteins by macrocycles

Abstract

The aggregation of amyloid proteins has been suggested to be the main cause of multiple human disorders; for example, amyloid β aggregates in Alzheimer's disease and α-synuclein aggregates in Parkinson's disease. In the search for therapeutic medicines, many molecules have been discovered and developed to modulate the aggregation of amyloid proteins. This century has witnessed the flourishing growth of supramolecular chemistry, and some biocompatible macrocycles have been proven to inhibit the aggregation of some amyloid proteins via host-guest interactions and could thus be used for the prevention or treatment of related diseases. Here, we review the application of macrocycles in modulating the aggregation of amyloid proteins.

In situmonitoring of protein aggregationviaclusteroluminescence

“…1B), the intensity ratio of CL to the emission of the tryptophan residue for the solid-state HEWL was bigger, suggesting the CTE effect. 26…”

“…1B), the intensity ratio of CL to the emission of the tryptophan residue for the solid-state HEWL was bigger, suggesting the CTE effect. 26 BSA is another protein that we tested. It has a molecular weight of 66 kDa and contained 583 amino acids with 8.4% aromatic amino acids, including phenylalanine (4.7%), tyrosine (3.4%) and tryptophan (0.3%).…”

14-3-3ζ Participates in the Phase Separation of Phosphorylated and Glycated Tau and Modulates the Physiological and Pathological Functions of Tau

“…A key pathological hallmark of neurodegenerative diseases is the abnormal accumulation of amyloid aggregates in cells, which leads to neuronal malfunction and cell death. − It was reported that liquid–liquid phase separation (LLPS) is closely regarded as an initial stage of amyloid aggregation, − such as Tau in Alzheimer’s disease (AD), TAR DNA-binding protein 43 (TDP-43), and FUS protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD).…”

Aggregation-Induced Emission (AIE), Life and Health

“…Protein aggregation is a multistep process that is associated with a growing number of human diseases, including neurodegenerative disorders, metabolic disorders, and cancers. − Solvatochromic probes have been developed to reveal protein misfolding in both test tubes and living cells, as represented by Prodan, SBD, and others. − In recent years, AIEgens have been applied to detect protein unfolding, oligomerization, and aggregation. − 1,2-Bis­[4-(3-sulfonatopropoxyl)­phenyl]-1,2-dipheny-lethene salt (BSPOTPE), a biocompatible AIEgen, was used to report insulin amyloid genesis . BSPOTPE exhibits significant fluorescence activation that correlates with insulin nucleation, elongation, and equilibrium phases, thus enabling the assessment of the amyloid genesis kinetics.…”