2003
DOI: 10.1021/bi027348m
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Inhibition of Tau Polymerization by Its Carboxy-Terminal Caspase Cleavage Fragment

Abstract: Abnormal aggregation of the microtubule-associated protein, tau, occurs in many neurodegenerative diseases, making it important to understand the mechanisms of tau polymerization. Previous work has indicated that the C-terminal region of tau inhibits polymerization in vitro, and a growing body of evidence implicates caspase cleavage of tau at Asp 421 in the C-terminus as an important inducer of tau polymerization in Alzheimer's disease. In the present study, we provide evidence that the C-terminal peptide frag… Show more

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Cited by 136 publications
(117 citation statements)
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“…The MC1 conformation may involve the intramolecular interaction between the N-and C-termini of tau (folded conformation). Caspase-cleavage of tau may initiate the MC1 conformation by removing a portion of the C-terminus that inhibits tau aggregation in vitro (46), and allowing tau to adopt this conformation.…”
Section: Discussionmentioning
confidence: 99%
“…The MC1 conformation may involve the intramolecular interaction between the N-and C-termini of tau (folded conformation). Caspase-cleavage of tau may initiate the MC1 conformation by removing a portion of the C-terminus that inhibits tau aggregation in vitro (46), and allowing tau to adopt this conformation.…”
Section: Discussionmentioning
confidence: 99%
“…C-terminal residues would be compatible with an amphiphilic R-helix which could interact with other domains of tau or partners of tau (9,11). The hexapeptide motifs in R2 and R3 (Figure 1) are predicted to form extended structure, ready to enter -sheet interactions.…”
Section: Discussionmentioning
confidence: 99%
“…Neurons with active caspase-3 often showed Asp421-cleaved tau. Caspase-3 cleavage of tau is thought to induce abnormal conformations by removing part of the C-terminal region, which is essential to inhibit tau aggregation in vitro (29,30). Although early apoptosis also may represent a developmental-related phenomenon (11), it is clear that the cleavage of tau is a toxic process with potentially important neurodegenerative repercussions.…”
Section: A P O P T O S I S I N a T R A N S G E N I C M O D E L O F T mentioning
confidence: 99%