Scientists reveal a new supramolecular therapy that protects human neurons against damages that offers new hope for the treatment of Alzheimer’s and related neurodegenerative diseases.
Study: Supramolecular copolymerization of glycopeptide east and amyloid peptides improves Neuron’s survival. Image Credit: Shutterstock AI Generator / Shutterstock.com
A recent study published in the Journal of the American Chemical Society Investigates the role of biocompatible peptide amphiles in preventing the misfolding and aggregation of proteins coupled to neurodegeneration.
Important pathological characteristics of neurodegenerative diseases
Neurodegenerative diseases (NDS) are characterized by the death of neurons, which leads to serious motor and cognitive impairment. The prevalence of NDS, including Parkinson’s disease (PD), Alzheimer’s disease (AD) and dementia, continues to rise worldwide, increasing the burden on global healthcare systems.
Proteinaggregation, such as amyloid beta (AP) and Tau, is characteristic of AD, while alpha synuclein aggregation occurs in PD. Proteinaggregation leads to the formation of amyloid protofilaments that clustate in amyloid fibrillen, which deposit at different locations in the cell.
Current treatment strategies for NDS include the braking of protein congregation formation, eliminating incorrectly folded proteins and changing cellular responses to manage simultaneous damage, such as oxidative stress.
Innovative approaches to treat NDS
Previous studies have reported the therapeutic benefits of supramolecular self-assembly of materials, in particular nanom materials, due to non-covalent interactions. Peptide -based supramolecular materials are also associated with various affordable properties for biomedical applications, including superior biocompatibility, biological availability and modularity compared to conventional peptides and proteins.
Structural parts such as amino acid sequence or the assembly environment of peptide amphiles (PAS) can be modified to change the strength of their hydrogen bridges and various morphological characteristics. Earlier, researchers reported the copolymerization capacity of PA-nanove fibers with different soluble peptid seasons to form a metastable supramolecular assembly that could improve the release of therapeutic peptides to save AP-related neurotoxicity.
Trehalose, a non -reducing, non -loaded disaccharide, has recently been investigated as a proteinchaperone that can protect proteins against misfolding, denaturation and aggregation. Trehalose also activates autophagia and reduces the accumulation of proteinaggregats, which improves neurotoxicity.
About the study
The current study is investigating the potential neuroprotective effects of Trehalose-PA (TPA) when saving amyloid-related neurodegeneration. Researchers stated the hypothesis that functionalization with trehalose TPAs would enable amyloid aggregation and stabilize the phenotypes of neurons that are influenced by amyloid-related neurotoxicity.
Different computational methods were used to examine interactions between non-finalized pass and amyloid beta 1-42 peptide (Aβ42) to clear up their ability to prevent amyloid aggregation. The therapeutic potential of TPAs was further assessed in vitro The use of neurons derived from people induced pluripotent stem cells (IPSCs) to determine their efficacy in protecting cells against neurotoxicity induced by Aβ42.
Therapeutic activity of Neurodegenerative diseases
Palmitoyl-VVAAEE (E2) was selected as the non-finalized backbone PA because of his superior biocompatibility and capacity to present bioactive motifs with an optimized density for neural application. TPAs were synthesized by conjugeren and then functioning a lysinese idu on the C-Terminus of E2.
Synchrotron Small X-ray spread (SAXS) was used to analyze E2 and TPA assemblies in glowed and non-annualized circumstances. E2 formed filamentous nanostructures in both circumstances, while not -an adorned TPA formed nanove fibers and formed a glowed TPA small micellar aggregates. The width of TPA -Nanove fibers was smaller than that of E2 -Nanove fibers.
Circular Dichroism (CD) Spectroscopy, solution synchrotron wide angle X-ray (WAXS) and Fourier-Transform Infrared spectroscopy (FT-IR) Analyzes revealed a higher degree of deprotonation of the Glutamicziduen in TPAAsiduen in TPAAsiduen. Cryogenic transmission-electron microscopy (Cryo-Tem) and negative coloring TEM confirmed the spectroscopic results, indicating that both E2 with or without glow-turned nanove fibers formed.
Variable temperature (VT) experiments revealed that the melting point of E2 assemblies was above 80 ° C. Further heating up to 90 ° C ensured that the β-plate signature of E2 disappears.
The TPA assembly was stable at 50 ° C, where the signature of the β plate began to shrink at 65 ° C, suggesting that TPA-Filamental Assemblies at low temperatures are metastable kinetic supramolecular structures. In addition, TPA-supramolecular assemblies were found to change the aggregation of Aβ42 and TPA-Aβ42 interactions that changed the morphology of the nanostructure.
Human motor neurons (MNS) remained feasible after treatment with 30 μm or less TPA. Monomere Aβ42 was incubated at 37 ° C for 16 hours to induce Aβ42 toxicity, after which four experimental TPA assemblies reduced cell death, which suggests that different rescue levels. In particular, non -tpa achieved the most effective rescue by reducing Aβ42 neurotoxicity.
Supramolecular nanostructures are an interesting target for therapeutic strategies in neurodegenerative diseases such as Alzheimer’s disease and amyotrophe lateral sclerosis. “
Journal References:
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GAO, Z., Qiu, R., Dave, Dr, et al. (2025) Supramolecular copolymerization of glycopeptide eagifils and amyloid peptides improves Neuron’s survival. Journal of the American Chemical Society. DOI: 10.1021/Jacs.5C00105.