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Molecular aging of tau: disulfide‐independent aggregation and non‐enzymatic degradation in vitro and in vivo
Author(s) -
Watanabe Atsushi,
Hong WonKyoung,
Dohmae Naoshi,
Takio Koji,
MorishimaKawashima Maho,
Ihara Yasuo
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02611.x
Subject(s) - deamidation , in vivo , chemistry , molecular mass , isomerization , biochemistry , succinimide , in vitro , enzyme , cleavage (geology) , tau protein , biophysics , stereochemistry , alzheimer's disease , biology , medicine , paleontology , microbiology and biotechnology , disease , pathology , fracture (geology) , catalysis
Smearing from high‐molecular‐mass regions to low‐molecular‐mass regions on western blot is the most striking observation of the tau making up paired helical filaments in brain tissues affected by Alzheimer's disease. Because our previous study showed site‐specific deamidation/isomerization in the smeared tau in vivo , a feature of protein aging, recombinant tau was subjected to prolonged (up to 90 days) in vitro incubation. Carboxymethylated tau at ∼50 kDa gradually disappeared and was converted to dimers and to high‐ and low‐molecular‐mass smearing. In addition, the same site‐specific deamidation/isomerization as previously identified in the smeared tau in vivo emerged. Most importantly, tau was spontaneously degraded, generating fragments that start from bulky residues next to asparaginyl residues. This spontaneous degradation of tau probably represents non‐enzymatic cleavage through the formation of succinimide intermediates. Similar degradation products starting from the bulky residues next to asparaginyl residues were found in the smeared tau in vivo partially purified from the homogenates from Alzheimer's disease brains.