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Tau, tangles, and Alzheimer's disease
Lester I Binder1, Angela L Guillozet-Bongaarts, Francisco Garcia-Sierra
1Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611, USA. l-binder@northwestern.edu
Biochimica Et Biophysica Acta
|December 24, 2004
Summary
Neurofibrillary tangles (NFT) form from tau protein aggregates. Specific truncations of tau, possibly from caspase activity, drive its ordered polymerization into filaments.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Neurofibrillary tangles (NFTs) are key pathological hallmarks of neurodegenerative diseases.
- These tangles are primarily composed of aggregated tau protein, a microtubule-associated protein.
- Tau protein undergoes significant post-translational modifications, including phosphorylation and truncation, during aggregation.
Purpose of the Study:
- To review the evidence for ordered truncation patterns in tau protein.
- To explore the influence of these truncations on tau conformation and polymerization.
- To discuss the potential role of caspases in tau truncation within the apoptotic cascade.
Main Methods:
- Literature review of studies on tau protein structure and aggregation.
- Analysis of experimental data on tau truncations and their effects.
- Examination of biochemical pathways involved in tau modification.
Main Results:
- Tau protein undergoes multiple truncations at both amino- and carboxy-termini.
- These truncations significantly alter tau conformation, promoting polymerization into fibrils.
- Evidence suggests an orderly pattern to these truncations, potentially mediated by caspases.
Conclusions:
- Ordered tau truncations are critical determinants of neurofibrillary tangle formation.
- Understanding these truncation events offers insights into disease pathogenesis.
- Targeting caspase-mediated tau cleavage may represent a therapeutic strategy.