Amyloid-β-regulated gene circuits for programmable Alzheimer's disease therapy.

ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disease characterized in part by the accumulation of the protein amyloid-β (Aβ). Monoclonal antibodies (mAbs) that target Aβ for clearance from the brain have received FDA approval; however, these therapies are accompanied by serious side effects, and their cognitive benefit for patients remains of tremendous debate. Here, we present a potential engineered cell therapy for AD in which we enlist cells of the central nervous system as programmable agents for sculpting the neurodegenerative niche toward one that mitigates glial reactivity and neuronal loss. We constructed a suite of Aβ-sensitive synthetic Notch (synNotch) receptors from clinically tested anti-Aβ mAbs and show that cells expressing these receptors can recognize synthetic Aβ₄

SUBMITTER: Spetz MR 

PROVIDER: S-EPMC11952467 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature