Functional domains on chemically modified tau protein

Area of Science:

• Neuroscience
• Biochemistry
• Cell Biology

Background:

• Neurofibrillary tangles, primarily composed of paired helical filaments (PHFs), are hallmarks of Alzheimer's disease.
• The microtubule-associated protein tau is a key structural component of these filaments.
• Understanding tau protein's aberrant behavior is crucial for Alzheimer's research.

Purpose of the Study:

• To investigate the effects of chemical modification on tau protein's assembly properties.
• To explore how altering tau protein structure influences its interaction with tubulin and its self-assembly.
• To gain insights into the anomalous interactions of tau in Alzheimer's disease.

Main Methods:

• Selective carbamoylation of brain tau protein using potassium cyanate (KCNO).
• In vitro microtubule polymerization assays to assess tubulin assembly capacity of modified tau.
• Ultrastructural analysis of polymers formed by carbamoylated tau protein.

Main Results:

• Carbamoylation irreversibly modified lysine residues on tau protein.
• The ability of chemically modified tau to induce tubulin assembly decreased with increasing carbamoylation.
• Carbamoylated tau protein self-assembled into PHF-like structures at concentrations above 1.0 mg/ml.

Conclusions:

• Chemical modification of tau protein alters its functional properties.
• Carbamoylated tau protein can form structures resembling PHFs, suggesting a potential mechanism in Alzheimer's disease.
• These findings provide new insights into the abnormal tau interactions implicated in Alzheimer's disease.