An explicitly designed paratope of amyloid-β prevents neuronal apoptosis in vitro and hippocampal damage in rat brain

Abstract

Herein, the therapeutic potentials of an explicitly designed peptide probe are systematically illuminated in vitro and in vivo against Aβ aggregation. The probe demonstrates remarkable potency for attenuating neurotoxicity and hippocampal damage.

Peptide backbone modifications of amyloid β (1–40) impact fibrillation behavior and neuronal toxicity

“…The protective behavior of N -Me-F , N -Me-L and N -Me-F/L counteracting cytotoxicity is expressed in the assay measuring caspase-3 activity, where they significantly decrease caspase-3 activation compared to the WT and partly to the control. This is in alignment with other N -methylated peptides in the literature 70 .…”

Delineating the Role of GxxxG Motif in Amyloidogenesis: A New Perspective in Targeting Amyloid-Beta Mediated AD Pathogenesis

“…Recent studies have elucidated the dock-lock mechanism of fibril formation, where unstructured Aβ monomers transiently associate with the fibril surface before undergoing a slower conformational rearrangement and incorporating into the primary fibril lattice. − This process, involving the central K16-A21 and C-terminal M35-V40 regions, plays a critical role in fibrillation and presents a potential avenue for inhibiting amyloidosis. Remarkably, our recent investigation employing a synthetic paratope, SP1, has demonstrated selective binding to the LVFFA epitope, a crucial amyloidogenic region of Aβ peptide . Furthermore, SP1 effectively disaggregated preformed fibrils of Aβ40, leading to the formation of nontoxic species.…”

“…Remarkably, our recent investigation employing a synthetic paratope, SP1, has demonstrated selective binding to the LVFFA epitope, a crucial amyloidogenic region of Aβ peptide. 123 Furthermore, SP1 effectively disaggregated preformed fibrils of Aβ40, leading to the formation of nontoxic species. Solution NMR analysis revealed that SP1 disrupts the essential dock-lock interactions of monomeric Aβ, suggesting molecular interference in the critical domain.…”

“…So far, most of the design strategies include short peptide sequence analogous to part of the native sequence of the protein or peptide responsible for fibril formation. − This approach is based on the fact that the short peptide fragments would self-recognize and thereby should bind to the homologous sequence in the native protein. The most popular approach for the inhibition of Aβ amyloidogenesis have been the design of peptides derived from the central hydrophobic cluster (L17-A21) of Aβ. − Since, amyloid fibrils usually adopt a cross β-structure, structure-based agents such as β-sheet breakers have also been formulated to inhibit fibril formation. − These inhibitory peptides are targeted to disrupt β-sheets by blocking the hydrogen bond formation between β-strands. In addition to peptide mimics, alterations in short peptides such as N -methylation and peptide cyclization have shown enhanced conformational stability with significantly increased inhibitory effect on amyloid aggregation. , …”

A critical review on emerging photoactive porous materials for sulfide oxidation and sulfur mustard decontamination

“…Many materials have been employed to detoxify sulfur mustard and its analogous derivatives; in this context, owing to its attenable functionality, superior chemical and thermal stability, and enhanced porosity, POPs emerge as a judicious choice. 97 POPs are a class of advanced functional materials with structural tailorability, inherent porosity, and high flexibility, which have served for several applications like CO 2 capture, 98,99 CO 2 reduction to solar fuels, 100,101 biomass valorisation, 102,103 organic transformation reactions, 104,105 CO 2 fixation, 99 gas and liquid separation, 106 water purification, 107,108 energy storage, 109 chemo-and biosensing 110 and HD decontamination [111][112][113][114][115] etc. (Fig.…”