Chemical and Structural Biology at the Frontiers of Rare Neurological and Neurometabolic Diseases

Rare neurological and neurometabolic diseases are often characterized by complex molecular etiologies and limited therapeutic options, largely due to gaps in our understanding of their underlying mechanisms. Chemical and structural biology provide powerful, complementary approaches to address these challenges. By revealing the three-dimensional structures, dynamic interactions, and chemical properties of biomolecules involved in disease processes, these disciplines enable the identification of novel targets and pathways. Recent advances in cryo-electron microscopy, NMR spectroscopy, X-ray crystallography, and chemical probe development have opened new frontiers in the study of protein misfolding, aggregation, and enzymatic dysfunctions associated with rare neurodegenerative, neurodevelopmental and neurometabolic disorders.

Rare neurological and neurometabolic diseases remain among the most challenging conditions to diagnose and treat, due to their low prevalence, clinical variability, and limited molecular characterization. Many of these disorders are linked to mutations or dysfunctions in proteins and enzymes whose structures and biochemical properties are still poorly understood. This lack of molecular insight hampers the development of targeted therapies and biomarkers.

This Special Issue aims to showcase interdisciplinary contributions that leverage chemical and structural biology to deepen our molecular understanding and accelerate the development of innovative diagnostic and therapeutic strategies for rare neurological and neurometabolic conditions. By combining high-resolution structural techniques (e.g., cryo-EM, NMR, X-ray crystallography) with chemical biology tools (e.g., small-molecule probes, bioorthogonal labeling, activity-based profiling), researchers can uncover the molecular mechanisms driving disease progression and identify novel therapeutic strategies.

To achieve this, we aim to gather interdisciplinary contributions that apply these approaches to elucidate protein misfolding, aggregation, enzymatic dysfunction, and molecular interactions in rare neurodegenerative, and neurodevelopmental and neurometabolic disorders. This will foster a deeper understanding of disease biology and promote innovation in diagnostics and drug discovery.

This collection seeks to foster interdisciplinary dialogue and promote translational research in the field of rare neurological and neurometabolic disorders. We invite contributions that investigate the molecular basis of these disorders through the characterization of protein structures, enzymatic mechanisms, and biomolecular interactions. Specific themes include protein misfolding and aggregation, structure-based drug design, chemical probes for functional analysis, and integrative approaches combining structural data with omics technologies.

Studies integrating structural data with chemical biology, omics technologies, or computational modeling are particularly encouraged. Specific themes include, but are not limited to:

1. High-resolution structural studies of disease-related biomolecules
2. Mechanistic insights into neurotoxicity, metabolic dysregulation, and cellular dysfunction
3. Structure-based drug discovery and therapeutic innovation
4. Novel methodologies in structural and chemical neurobiology and neurometabolism

Article types and fees

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

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• ... 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
• Data Report
• Editorial
• FAIR² Data
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review

Keywords: Chemical Biology, Structural Biology, Rare Neurological Disorders, Rare Neurometabolic Disorders;, Molecular Machanisms;, Therapeutic Innovations, Chemical neurobiology, Rare neurometabolic diseases, Protein misfolding, structure-based drug discovery

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.