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Target intelligence / Profile preview
Neurofibrillary Tangles (NFTs)
- Target
- NFTs
- Molecular classification
- Protein aggregates, Intracellular inclusions
01
Overview
Neurofibrillary tangles (NFTs) are abnormal, intracellular aggregates of hyperphosphorylated tau protein found within neurons. They are a fundamental neuropathological hallmark of Alzheimer’s disease and other neurodegenerative disorders known as tauopathies. NFTs disrupt normal cellular function by impairing microtubule function and axonal transport, leading to synaptic dysfunction and neuronal death. The formation and spread of NFTs correlate with the progression and severity of cognitive decline.
- Other names
- Paired Helical FilamentsPHF-tauTau tangles
02
Mechanism of action
N/A
03
Biological functions
Disruption of microtubule functionImpaired axonal transportSynaptic dysfunctionNeuronal death
04
Disease associations
Alzheimer's diseaseTauopathiesPick's diseaseProgressive supranuclear palsy (PSP)Corticobasal degeneration (CBD)Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17)
05
Safety considerations
Targeting intracellular aggregates is challenging for drug deliveryPotential for off-target effects due to tau presence in healthy neuronsComplexity of tau isoforms and phosphorylation statesReversing established tangles may be difficultImmunotherapy approaches to clearing tau aggregates may have inflammatory side effects
06
Biomarkers
Hyperphosphorylated tauPHF-tau levels in CSFNFT density in brain tissue (post-mortem)Tau PET imaging
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