Tau Conformational Change-Triggered Membrane Disruption

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

Mechanistic description

Nanobodies that recognize specific tau conformational epitopes and simultaneously possess membrane-disrupting activity could achieve selective penetration by binding surface-exposed pathological tau and then disrupting the associated membrane locally.

Evidence for (5)

  • 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

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

    PMID:27940599 2017 Cold Spring Harb Perspect Med

  • ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids.

    PMID:34314701 2021 Cell

  • The six brain-specific TAU isoforms and their role in Alzheimer's disease and related neurodegenerative dementia syndromes.

    PMID:38556838 2024 Alzheimers Dement

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