Structure-based design of nanobodies that inhibit seeding of Alzheimer's patient-extracted tau fibrils.

ABSTRACT: Despite much effort, antibody therapies for Alzheimer's disease (AD) have shown limited efficacy. Challenges to the rational design of effective antibodies include the difficulty of achieving specific affinity to critical targets, poor expression, and antibody aggregation caused by buried charges and unstructured loops. To overcome these challenges, we grafted previously determined sequences of fibril-capping amyloid inhibitors onto a camel heavy chain antibody scaffold. These sequences were designed to cap fibrils of tau, known to form the neurofibrillary tangles of AD, thereby preventing fibril elongation. The nanobodies grafted with capping inhibitors blocked tau aggregation in biosensor cells seeded with postmortem brain extracts from AD and progressive supranuclear palsy (PSP) patient

SUBMITTER: Abskharon R 

PROVIDER: S-EPMC10576031 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature