Protective Effect of a Hexapeptide Derived from Rotifer-Specific SCO-Spondin Against Beta-Amyloid Toxicity

TL;DR

A hexapeptide derived from a rotifer protein protects against beta-amyloid toxicity, which is linked to neurodegenerative diseases like Alzheimer's.

Contribution

The study identifies a novel hexapeptide, DSSNDL, with protective effects against beta-amyloid toxicity in both in vitro and in vivo models.

Findings

DSSNDL showed significant protection against beta-amyloid toxicity in differentiated neuro-type cells and rotifers.

DSSNDL interacts with beta-amyloid aggregates, altering their properties and potentially inhibiting their toxicity.

The hexapeptide is present in both rotifer and human proteomes, suggesting potential translational relevance.

Abstract

The Rotimer (rotifer-specific biopolymer) like SCO-spondin (R-SSPO/1), predicted as the main component of this biopolymer, is an adequate base for the design of functional small peptides. This macromolecule is interactive and protective against neurotoxic human-type beta-amyloid 1-42 aggregates (agg-Aβ). The current work presents biological investigations and predictable molecular interaction analysis of DSSNDL and PNCRDGSDE peptides that were synthesized based on the sequences of R-SSPO/1. Viability assays (NADH-dependent cellular reduction capacity, intracellular esterase activity, and motility) were performed on differentiated neuro-type cell cultures (SH-SY5Y and PC12) and on Rotimer-depleted rotifers (Euchlanis dilatata and Lecane bulla). A control peptide (STTRPTGTT), not found in Rotimer, was also included in the study. All three peptides are present in both rotifer and human proteomes. Among these small molecules, DSSNDL showed a significant protective effect against the toxicity of agg-Aβ both in vitro and in vivo and presumably interacted with its aggregates. The stagogram analysis of amyloid–peptide complexes and the possible bonding competition of these small molecules against aggregation-specific dyes on agg-Aβ surface suggest that DSSNDL affects the properties of these neurotoxic macromolecules. This effective hexapeptide can serve as a promising candidate for further investigations into the inactivation of beta-amyloid toxicity.

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