Tau, tangles, and Alzheimer's disease.
Neurofibrillary tangles (NFT) are comprised of the microtubule-associated protein tau, in the form of filamentous aggregates. In addition to the well-known changes in phosphorylation state, tau undergoes multiple truncations and shifts in conformation as it transforms from an unfolded monomer to the structured polymer characteristic of NFT. Truncations at both the amino- and carboxy-termini directly influence the conformation into which the molecule folds, and hence the ability of tau to polymerize into fibrils. Certain of these truncations may be due to cleavage by caspases as part of the apoptotic cascade. In this review, we discuss evidence that strongly suggests that these truncations occur in an orderly pattern and directly influence the ability of tau to polymerize into filaments.
Binder
Lester I
LI
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611, USA. l-binder@northwestern.edu
Guillozet-Bongaarts
Angela L
AL
Garcia-Sierra
Francisco
F
Berry
Robert W
RW
D000544:Alzheimer Disease / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D016874:Neurofibrillary Tangles / Q000378:metabolism*; D009454:Neurofibrils / Q000737:chemistry; D011487:Protein Conformation; D016875:tau Proteins / Q000737:chemistry*
D016875:tau Proteins; D020169:Caspases