Structural and Functional Insights into CNS Targets: From Mechanisms to Small Molecule Interventions

The central nervous system (CNS) remains one of the most intricate and challenging frontiers in biomedical research due to its structural complexity, cellular heterogeneity, and the selective permeability of the blood–brain barrier. Disorders of the CNS, including neurodegenerative, neuroinflammatory, and psychiatric conditions, pose a significant global health burden; yet the development of safe and effective therapeutics continues to be a formidable challenge. Despite progress in structural and mechanistic biology, the successful translation of these insights into small‑molecule therapeutics remains limited. A deeper understanding of CNS target biology and its structural framework is therefore essential for enabling rational drug discovery and intervention.

This Research Topic aims to bridge the gap between mechanistic understanding and translational application by highlighting recent advances in the structural and functional characterization of key CNS targets. The focus will be on elucidating the molecular mechanisms that govern protein structure, signaling, and regulation within the CNS, and on how these insights inform small‑molecule design. We encourage submissions that provide novel perspectives on structure–function relationships, allosteric modulation, conformational dynamics, and structure‑guided ligand optimization. The Topic seeks to integrate discoveries from basic neuroscience, structural biology, and medicinal chemistry to accelerate CNS drug discovery.

This collection welcomes contributions that include, but are not limited to:

• Structural and biophysical characterization of CNS proteins (e.g., kinases, GPCRs, ion channels, transporters).
• Mechanistic studies linking molecular architecture to disease‑associated dysfunction.
• Computational modeling, virtual screening, and molecular dynamics simulations for CNS target exploration.
• Medicinal chemistry efforts focused on optimizing small‑molecule potency, selectivity, and brain penetration.
• Innovative approaches to overcoming CNS‑specific challenges such as target selectivity, BBB permeability, and drug metabolism.
• Chemical biology, fragment‑based, or structure‑based drug design targeting CNS‑relevant pathways.
• Translational studies connecting molecular insights to pharmacological or behavioral outcomes.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: CNS drug discovery, Structure–function relationships, Blood–brain barrier permeability, Allosteric modulation, Structure‑guided small‑molecule design, ADME properties

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.