¶ Overview
MAPT is a protein involved in cellular processes relevant to neurodegeneration.
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- Protein Name: MAPT - Microtubule-Associated Protein Tau
- UniProt ID: P10636
- Gene: MAPT
- Molecular Weight: 45-65 kDa (isoform dependent)
- Protein Class: Cytoskeletal protein, Microtubule stabilizer
- Tissue Expression: Neurons (axons), primarily brain, also heart and kidney
¶ Function
MAPT (tau) is a neuronal microtubule-associated protein that plays a critical role in microtubule stabilization and axonal transport. Key functions include: [7]
- Microtubule assembly: Tau promotes microtubule polymerization and stability
- Axonal transport: Tau facilitates vesicle and organelle transport along axons
- Neuronal polarity: Tau helps establish and maintain axonal identity
- Synaptic function: Tau is involved in synaptic plasticity and memory formation
Tau is encoded by a single gene on chromosome 17q21 with multiple splice isoforms ranging from 352 to 441 amino acids. Alternative splicing produces six isoforms in adult brain.
¶ Tau Pathology in Neurodegeneration
¶ Alzheimer Disease
Tau is a central player in Alzheimer's disease pathogenesis:
- Neurofibrillary tangles (NFTs): Hyperphosphorylated tau forms insoluble aggregates in neurons
- Tau spreading: Pathological tau propagates between connected neurons
- Correlation with cognitive decline: NFT burden correlates strongly with cognitive impairment
- Tau hypothesis: Tau pathology may be downstream of amyloid but drives neurodegeneration
¶ Other Tauopathies
- Frontotemporal Dementia (FTD): Tau mutations cause familial FTD
- Chronic Traumatic Encephalopathy (CTE): Repetitive head trauma causes tau pathology
- Progressive Supranuclear Palsy (PSP): 4R tau isoforms accumulate
- Corticobasal Degeneration (CBD): Mixed 3R/4R tau pathology
Post-Trans##lational Modifications
Tau undergoes numerous post-translational modifications:
- Phosphorylation: >45 phosphorylation sites; hyperphosphorylation in disease
- Acetylation: Promotes aggregation
- Truncation: C-terminal fragments are more aggregation-prone
- O-GlcNAcylation: May be protective
- Sumoylation: Promotes aggregation
¶ Therapeutic Strategies
- Anti-aggregation drugs: Small molecules to prevent tau aggregation
- Tau phosphorylation inhibitors: Kinase inhibitors (GSK-3β, CDK5)
- Tau immunotherapy: Antibodies targeting tau (active and passive)
- Microtubule stabilizers: Paclitaxel analogs
- Tau degradation: UCHL1, autophagy enhancers
¶ Clinical Biomarkers
- CSF total tau: Elevated in AD
- CSF phospho-tau: More specific for AD
- PET tau tracers: Florbetaben, flortaucipir for in vivo imaging
¶ Cross-Links
¶ Key Publications
- Mandelkow E et al., Tau physiology and pathology (2007)
- Ballatore C et al., Tau-mediated neurodegeneration (2007)
- Goedert M et al., Tau protein in Alzheimer's disease (2006)
¶ See Also
- Neurodegeneration — General mechanisms
¶ External Links
¶ See Also
¶ External Links
¶ References
¶ Additional references
Ballatore C et al. Tau-mediated neurodegeneration (2007). 2007. ↩︎
Goedert M et al. Tau protein in Alzheimer's disease (2006). 2006. ↩︎
Weingarten MD et al. Tau as a regulating factor (1975). 1975. ↩︎
Garcia ML et al. Tau/Fyn phosphorylation (1999). 1999. ↩︎
Cohen TJ et al. Tau post-translational modifications (2011). 2011. ↩︎
Gong CX et al. Tau phosphorylation in AD (2005). 2005. ↩︎
Avila J et al. Tau function in neurons (2004). 2004. ↩︎