CNS Disease Cell Models and Targeted Drug Discovery

The field of Central Nervous System (CNS) disease research is currently undergoing a transformative phase with the advent of targeted protein degradation (TPD) strategies. TPD is revolutionizing drug discovery by shifting the focus from traditional functional inhibitors to proteolytic degraders, which facilitate the destruction of disease-causing proteins through the ubiquitin-proteasomal and endosome-lysosomal pathways. Despite the promising potential of TPD, there are significant challenges in developing CNS disease-targeted therapies. Neurons, being post-mitotic cells, pose difficulties in culture modeling for drug studies. Additionally, the blood-brain barrier (BBB) presents a formidable obstacle, preventing drugs from effectively reaching and acting on targeted proteins within the brain. Furthermore, the degradation pathways for many CNS disease-causing proteins remain inadequately understood, resulting in a limited number of degraders targeting neurological disease proteins. Recent studies have highlighted the need for innovative approaches to overcome these barriers, yet comprehensive solutions are still lacking.

This research topic aims to explore and address the challenges associated with CNS disease-targeted drug discovery, particularly focusing on the development and application of TPD strategies. The primary objectives include investigating the degradation pathways of CNS disease-causing proteins, enhancing the understanding of BBB models for drug delivery, and advancing CNS disease cell and organoid models. By addressing these areas, the research seeks to expand the repertoire of therapeutic degraders and improve the efficacy of CNS disease-targeted treatments.

To gather further insights in the realm of CNS disease-targeted drug discovery, we welcome articles addressing, but not limited to, the following themes:
- Development and application of CNS disease cell and organoid models.
- Exploration of degradation pathways for CNS disease-causing proteins.
- Innovations in blood-brain barrier models for enhanced drug delivery.
- Advances in CNS disease-targeted drug discovery, including TPD degraders and protein functional inhibitors.