Decoding neurodegenerative mechanisms: from in vitro models to the bedside - Insights from the BraYn Conference 2025

Neurodegenerative diseases like Alzheimer's, Parkinson's, and Huntington's represent an increasing global health burden. Their complex molecular mechanisms lead to progressive neuronal dysfunction and loss, often decades before symptom onset, ultimately causing severe cognitive decline. Despite extensive scientific effort, precise cellular and molecular mechanisms remain incompletely understood, and effective disease-modifying therapies are lacking. A major limitation is the scarcity of reliable, translationally relevant experimental models capable of faithfully recapitulating human neurodegeneration.

This editorial project has been launched in conjunction with the eighth BraYn Conference, held at The Polytechnic University of Turin (October 29-31).

This Research Topic aims to gather diverse, high-impact studies that bridge fundamental cellular insights with translational and clinical perspectives. Contributions will highlight how state-of-the-art in vitro (induced pluripotent stem cells (iPSCs), brain organoids, microfluidic platforms, 3D culture systems) and in vivo (mice, zebrafish, Drosophila, C. elegans) models can unravel key pathological mechanisms such as synaptic dysfunction, protein aggregation, mitochondrial impairment, neuroinflammation, and cellular senescence. Integrative efforts connecting in vitro findings with in vivo and clinical data through cutting-edge technologies like omics-based profiling, high-content imaging, and computational modeling are particularly encouraged. Such approaches hold potential to capture patient-specific variability, enabling mechanistic studies of both genetic and sporadic disease forms, while also facilitating drug screening and accelerating biomarker discovery.

By fostering dialogue across basic, translational, and clinical research, these collected studies will underscore the importance of data integration from cellular mechanisms to clinical outcomes. They will highlight how basic and cellular-level research is moving beyond mere mechanism description toward deeper, more reliable understanding of disease molecular mechanisms and their interplay, laying the foundation for next-generation, tailored interventions that consider individual patient profiles.

Ultimately, this Research Topic emphasizes a precise goal: to decrease the gap between experimental models and clinical evidence in neurodegeneration research, increasing the applicability of diagnostic tools and therapeutic interventions. Through this multidisciplinary spectrum, "Decoding neurodegenerative mechanisms: from in vitro models to the bedside" reflects evolving cellular neuroscience as a driver for precision medicine in neurodegenerative diseases.

We encourage contributions on, but not limited to, the following subject areas:

- Investigating the fundamental pathological mechanisms of neurodegeneration, including synaptic dysfunction, protein aggregation, mitochondrial impairment, neuroinflammation, and cellular senescence.

- Exploring the utility and advancement of diverse experimental models, encompassing both state-of-the-art in vitro systems (e.g., iPSCs, organoids) and relevant in vivo models (e.g., mice, zebrafish).

- Employing integrative research approaches and cutting-edge technologies like omics-based profiling, high-content imaging, and computational modeling to connect cellular insights with clinical data.

- Facilitating translational and clinical applications, such as drug screening, biomarker discovery, and the development of patient-specific, precision medicine interventions.

- Decreasing the gap between experimental models and clinical evidence to enhance the applicability of diagnostic tools and therapeutic strategies in neurodegeneration research.