Alzheimer’s, in Los Angeles there is an innovative method to study the underlying mechanisms

A group of researchers from the Terasaki Institute for Biomedical Innovation in Los Angeles, California, has conducted an innovative study that provides us with new information on the complex and in some ways still mysterious mechanisms underlying Alzheimer’s diseasethe most common form of dementia that is estimated to account for between 50 and 80% of neurodegenerative diseases. In other words, it provides us with a cutting-edge study model that many other groups around the world can use to mimic as closely as possible what happens to neurons when they begin to be “suffocated” and inhibited by protein accumulations.

The research, titled “Effects of a Peptide-Based Hydrogel Matrix Mimicking Amyloid-β on the Phenotype of Neuronal Progenitor Cells,” represents a significant step toward better understanding the interaction between structures similar to amyloid – a fibrillar protein substance that accumulates in the skin and internal organs in localized or diffuse form and generates amyloidosis, including Alzheimer’s disease – and neuronal cells.

The research team, led by Natashya Falcone and co-authored by Tess Grett Mathes and Mahsa Monirizad, focused on the so-called Self-assembling peptide-based hydrogelknown for their versatility in reproducing the extracellular matrices of different microenvironments of study and interest. This is one of the new fronts of thetissue engineering at the crossroads of molecular and cellular biology, materials science and engineering. Peptides are obtained through processes of synthesis or partial hydrolysis, chemical or enzymatic, of some proteins. Treated in the right way, they have the ability, when they are in thermodynamic equilibrium, to spontaneously organize themselves into ordered and stable structures. They are therefore potentially very useful for tissue repair and regeneration interventions for the biomedicine of the future.

Alzheimer’s disease, as we have seen on many occasions, presents a complex challenge in neurodegeneration research. However, traditional two-dimensional (2D) models have limitations in capturing the complexity of the dynamics that lead to the development, sometimes over decades, of the disease. For this reason, through an innovative approach, the team has developed a multicomponent hydrogel structure called Col-HAMA-FFdesigned to mimic the amyloid-beta (β)-containing environment associated with Alzheimer’s disease.

The results of the study, recently published in the journal Acta Biomaterialiahighlight the formation of β-sheet structures – the second most common form of protein secondary structure, whose degenerative association has been identified as a phenomenon underlying numerous human diseases, just like in amyloidosis – inside the hydrogel matrix, mimicking the nanostructures of beta-amyloid proteins. By culturing healthy neural progenitor cells in this particular environment and comparing the results with those obtained in a matrix simulating the natural environment, the researchers observed elevated levels of markers of neuroinflammation And apoptosisthat is, of a particular type of cell death, the so-called programmed one.

“This indicates a significant impact of amyloid-like structures on the phenotypes and behaviors of neuronal progenitor cells,” he noted. ScienceDaily. Ali Khademhosseini, corresponding author of the study, explained that “this seminal work provides a promising basis for future investigations into the mechanisms of Alzheimer’s and for drug testing. By linking the 3D hydrogel models and the complexity of Alzheimer’s pathological nanostructures, we aim to understand this interaction on healthy neuronal cells to accelerate the development of effective therapeutic strategies”. Ultimately, the study represents a crucial step towards decoding the mysteries of cellular and biological environments very similar to those in which Alzheimer’s develops. beta-amyloid peptide, the major constituent of senile plaques considered – together with the hyperphosphorylated tau protein – at the basis of Alzheimer’s disease (the US FDA has just approved a promising new drug that tries to attack those tangles, the donanemab by Eli Lilly). It therefore marks a significant milestone in the search for innovative solutions to combat neurodegenerative diseases. Interestingly, without the basic memory of digital environments.