Phosphatidylserine-Targeting Nanobody Chimeras

MAPT molecular biology market 52% active
Composite
46%
Novelty
50%
Feasibility
50%
Impact
—
Mechanistic
50%
Druggability
50%
Safety
50%
Confidence
50%

Mechanistic description

Nanobodies engineered with phosphatidylserine-binding domains could selectively penetrate vesicles containing aggregated tau, as pathological tau aggregation disrupts membrane asymmetry and exposes PS on the inner leaflet.

Evidence for (5)

  • Interactions between Microtubule-Associated Protein Tau (MAPT) and Small Molecules.

    PMID:27940599 2017 Cold Spring Harb Perspect Med

  • MAPT mutations, tauopathy, and mechanisms of neurodegeneration.

    PMID:30742061 2019 Lab Invest

  • Tau-targeting antisense oligonucleotide MAPT(Rx) in mild Alzheimer's disease: a phase 1b, randomized, placebo-controlled trial.

    PMID:37095250 2023 Nat Med

  • Tau filaments with the Alzheimer fold in human MAPT mutants V337M and R406W.

    PMID:40044789 2025 Nat Struct Mol Biol

  • Isoform-specific patterns of tau burden and neuronal degeneration in MAPT-associated frontotemporal lobar degeneration.

    PMID:36066634 2022 Acta Neuropathol

Evidence against (3)

  • Alzheimer Disease: An Update on Pathobiology and Treatment Strategies.

    PMID:31564456 2019 Cell

  • Synergy between amyloid-β and tau in Alzheimer's disease.

    PMID:32778792 2020 Nat Neurosci

  • Cellular and pathological functions of tau.

    PMID:39014245 2024 Nat Rev Mol Cell Biol