Biochemical stress markers in neurodegeneration: Insights from 3D cellular models

Understanding the multifaceted nature of neurodegenerative disease (NDDs) remains a significant challenge due to the complex intracellular /intercellular phenomena. This review explores the latest findings about the biochemical stress markers within the complex landscape of NDDs, with a specific focus on novel 3D cell cultures. Recent research highlights the importance of structural complexity and cellular crosstalk which lead to responses resembling those observed in the brain. However, issues such as vascularization and shear stress (which affect experimental reproducibility) remain. Here we emphasize the role of biochemical stressors in cellular interactions and communication relevant to NDDs, highlighting the emerging opportunities coming from exosomes/extracellular vesicles and noncoding RNAs as biomarkers, alongside the usefulness of brain organoids in terms of translational relevance. By bridging the gap between molecular mechanisms and organ dysfunction, 3D models emerge as essential tools for the discovery of novel theragnostic biomarkers and for the development of targeted therapeutic strategies.