Abstract
Introduction
Nanobodies, or single-domain antibodies derived from camelid heavy-chain-only antibodies, have emerged as powerful tools in biomedical research and therapeutic development. Their small size, high specificity, tissue penetration capacity, stability, and production capacity can offer advantages over traditional therapeutic antibodies for neurological treatments.
Main Body
This review provides an overview of nanobody structural and biochemical features, new selection and engineering strategies, and current advances in nanobody humanization. We discuss the role of nanobodies in diagnostics, imaging, and therapeutics for neurological disorders, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy, and brain tumors. Special attention is given to recent breakthroughs enabling nanobody delivery to the central nervous system, including receptor-mediated transcytosis, intranasal administration, and intrabody engineering. In addition, we explore in silico nanobody discovery platforms powered by artificial intelligence, which accelerate the design of nanobody-antigen complexes.
Conclusion
These developments underscore the transformative potential of nanobodies as diagnostic probes and therapeutic agents for a broad range of neurodegenerative, inflammatory, infectious, and neoplastic diseases of the brain.