Inhibiting mTTR Aggregation/Fibrillation by a Chaperone-like Hydrophobic Amino Acid-Conjugated SPION

Abstract

Transthyretin (TTR) aggregation via misfolding of a mutant or wild-type protein leads to systemic or partial amyloidosis (ATTR). Here, we utilized variable biophysical assays to characterize two distinct aggregation pathways for mTTR (a synthesized monomer TTR incapable of association into a tetramer) at pH 4.3 and also pH 7.4 with agitation, referred to as mTTR aggregation and fibrillation, respectively. The findings suggest that early-stage conformational changes termed monomer activation here determine the aggregation pathway, resulting in developing either amorphous aggregates or well-organized fibrils. Less packed partially unfolded monomers consisting of more nonregular secondary structures that were rapidly produced via a mildly acidic condition form amorphous aggregates. Meanwhile, more hydrophobic and packed monomers consisting of rearranged β sheets and increased helical content developed well-organized fibrils. Conjugating superparamagnetic iron oxide nanoparticles (SPIONs) with leucine and glutamine (L-SPIONs and G-SPIONs in order) via a trimethoxysilane linker provided the chance to study the effect of hydrophobic/hydrophilic surfaces on mTTR aggregation. The results indicated a powerful inhibitory effect of hydrophobic L-SPIONs on both mTTR aggregation and fibrillation. Monomer depletion was introduced as the governing mechanism for inhibiting mTTR aggregation, while a chaperone-like property of L-SPIONs by maintaining an mTTR native structure and adsorbing oligomers suppressed the progression of further fibril formation.

Bivalent metal ions induce formation of α-synuclein fibril polymorphs with different cytotoxicities

“…The ATR-FTIR spectra recorded for α-Syn fibrils formed in the presence and absence of various cations and their deconvolution displayed in Fig. 3 indicate the distinctive bands at 1606, 1629, and 1684 cm −1 in the amide I region of all the fibril samples revealing the dominance of β sheets (at least 61%), which is in accordance with previous studies 22 – 25 . Furthermore, a band at 1660 cm −1 was detected in all the fibrils samples, which is attributed to the presence of β turns 23 .…”

Inhibition Of Tau Protein Aggregation By a Chaperone-like β-Boswellic Acid Conjugated To Gold Nanoparticles

“…In this instance, the protein aggregation kinetics will be accelerated or inhibited. 37 Inhibition of tau protein aggregation by employing metal NPs has been examined, suggesting that GNPs may also exert disaggregation activity. 35 Therefore, in the following investigation, the effects of hydrophobicity, size, and charged surface GNP-BA on the monomer of tau protein aggregation were examined.…”

“…As a result, in an NP–protein complex, protein binding to the surface of the NPs is not shocking. , The bonding may result in conformational changes in the adsorbed proteins, regardless of the state of the protein (from a folded or unfolded monomer to larger assemblies like fibrils). In this instance, the protein aggregation kinetics will be accelerated or inhibited …”

Microscopic Insights into the Mechanism of White Light Generation by Disruptive Interaction between Human Serum Albumin Amyloid Fibrils and Surfactant-AIEgen Nanorods

“…The generation of white light has been an area of active research, due to its potential applications in organic electronics and biophysical chemistry. − Its inherent mechanism is usually believed to involve a cascade energy transfer pathway in complex systems containing multiple emitting species; still, it is also possible that the observed white light is simply a sum of emissions in different spectral regions, from the components of the system. Of the various strategies for assembling multichromophoric systems for this purpose, surfactant-induced aggregation is convenient and reliable. − In recent times, this modality has been exploited to obtain aggregation-induced enhancement of emission (AIEE). − The study presented here explores the potential of one such aggregate in the design of novel white light-emitting platforms, in conjunction with protein amyloid fibrils. − The implications of amyloid fibrils in neurological diseases − prompted a frenzy of activity in the field of inhibition of aggregation and/or fibrillation. − More recently, however, more attention has been paid to the prospect of amyloid fibrils as functional biomaterials, , with potential applications in drug delivery, analyte sensing, and bioengineering and as templates for self-assembly . Hence, the domain has expanded from conventional disease-related fibril-forming proteins like amyloid protein and prion protein to globular proteins like myoglobin and albumins, ,, in which fibrillation can be induced under experimental conditions.…”