Cell Type and Isoform-Specific Mechanisms in Neurological, Neurodegenerative, and Neurodevelopmental Disorders

Neurogenetic disorders are characterized by extraordinary molecular and cellular complexity. Alternative splicing and isoform regulation shape the proteome of the human brain, while cell type–specific gene expression programs define neuronal identity and vulnerability. Disruption of these finely tuned processes has been implicated in conditions ranging from autism spectrum disorder and intellectual disability to Alzheimer’s and Parkinson’s disease. However, conventional bulk transcriptomics often masks these nuanced effects, limiting our ability to link genetic variation to functional mechanisms. Advances in single-cell, spatial, and long-read technologies now offer unprecedented resolution to interrogate isoform- and cell type–specific regulation in disease-relevant contexts.

The goal of this Research Topic is to address the gap in our understanding of how isoform- and cell type–specific regulation contributes to the etiology of neurological, neurodevelopmental, and neurodegenerative disorders. We aim to curate a collection of cutting-edge research that investigates transcriptomic diversity using bulk, single-cell, spatial, and long-read sequencing approaches. We envision contributions that not only reveal novel disease-associated isoforms and regulatory mechanisms but also demonstrate how isoform-level and cell type–specific insights can inform therapeutic development and precision medicine.

We welcome original research, methods papers, and reviews covering: Isoform diversity and alternative splicing in the brain; Cell type–specific transcriptomics in health and disease; Single-cell and spatial transcriptomic approaches; Long-read sequencing applications in isoform resolution; Functional studies linking isoform specificity to neuronal biology; Computational and AI-driven approaches for isoform discovery and interpretation; Translational insights into diagnostics or therapeutics. Contributors may submit original research articles, brief research reports, reviews, methods papers, and perspectives.

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
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• 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
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Alternative splicing, isoform specificity, cell type heterogeneity, neurodevelopmental disorders, neurodegeneration, transcriptomics, single-cell sequencing

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.