Zusammenfassung
1. Neurofibrillary tangles present in Alzheimer's disease and, in a
lower proportion, in aged brains are formed mainly by paired helical
filaments. The microtuble-associated protein tau is a major structural
component of these filaments. In order to increase our understanding of
the aberrant behaviour of tau protein leading to its assembly into
paired helical filaments, studies were carried out using chemical
modifications of brain tau protein.
2. Selective carbamoylation of tau with KCNO resulted in an irreversible
modification of lysine residues on tau protein. The capacity of
chemically modified tau protein to induce tubulin assembly, under
standard in vitro microtubule polymerization conditions, decreased
gradually in relation to the increase in concentration of the modifying
reagent.
3. Interestingly, carbamoylated tau protein exhibited the capacity to
self-assemble into polymeric structures resembling those of paired
helical filaments, after incubating the modified protein at
concentrations higher than 1.0 mg/ml, at 37-degrees-C with KCNO.
4. The nature of polymers obtained from cabamoylated tau protein was
analyzed by ultrastructural studies. The data provide new clues toward
our understanding of the anomalous interactions of tau in Alzheimer's
disease.
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