Application of engineered antibodies (scFvs and nanobodies) targeting pathological protein aggregates in Alzheimer's disease.

Introduction: The misfolding and aggregation of proteins are associated with various neurodegenerative diseases, such as Alzheimer's disease (AD). The small-molecule engineered antibodies, such as single-chain fragment variable (scFv) antibodies and nanobodies (Nbs), have gained attention in recent years due to their strong conformational specificity, ability to cross the blood-brain barrier (BBB), low immunogenicity, and enhanced proximity to active sites within aggregates.

Areas covered: We have reviewed recent advances in therapies involving scFvs and Nbs that efficiently and specifically target pathological protein aggregates. Relevant publications were searched for in MEDLINE, GOOGLE SCHOLAR, Elsevier ScienceDirect and Wiley Online Library.

Expert opinion: We reviewed the recent and specific targeting of pathological protein aggregates by scFvs and Nbs. These engineered antibodies can inhibit the aggregation or promote the disassembly of misfolded proteins by recognizing antigenic epitopes or through conformational specificity. Additionally, we discuss strategies for improving the effective application of engineered antibodies in treating AD. These technological strategies will lay the foundation for the clinical application of small-molecule antibody drugs in developing effective treatments for neurological diseases. Through rational application strategies, small-molecule engineered antibodies are expected to have significant potential in targeted therapy for neurological disorders.