title: Preservation of native conformation during aluminium-induced aggregation of tau protein.
abstract: Aluminium exposure has been shown to result in aggregation of microtubule-associated protein tau in vitro. In the light of recent observations that the native random structure of tau protein is maintained in its monomeric and dimeric states as well as in the paired helical filaments characteristic of Alzheimer's disease, it is likely that factors playing a causative role in neurofibrillary pathology would not drastically alter the native conformation of tau protein. We have studied the interaction of tau protein with aluminium using circular dichroism (CD) and 27Al NMR spectroscopy. The CD studies revealed a five-fold increase in the observed elipticity of the tau-aluminium assembly. The increase in elipticity was not associated with a change in the general conformation of the protein and was most likely due to an aggregation of the tau protein induced by aluminium. 27Al NMR spectroscopy confirmed the binding of aluminium to tau protein. Hyperphosphorylation of tau in Alzheimer's disease is known to be associated with defective microtubule assembly in this condition. Abnormally phosphorylated tau exists in a polymerized form in the paired helical filaments (PHF) which constitute the neurofibrillary tangles found in Alzheimer's disease. While it is hypothesized that its altered biophysical characteristics render abnormally phosphorylated tau resistant to proteolysis, causing the formation of stable deposits, the sequence of events resulting in the polymerization of tau are little understood, as are the additional factors or modifications required for this process. Based on the results of our spectroscopic studies, a model for the sequence of events occurring in neurofibrillary pathology is proposed.
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
authors.forename: T R
authors.initials: TR
authors.lastname: Madhav
authors.forename: S
authors.initials: S
authors.lastname: Vatsala
authors.forename: T
authors.initials: T
authors.lastname: Ramakrishna
authors.forename: J
authors.initials: J
authors.lastname: Ramesh
authors.forename: K R
authors.initials: KR
authors.lastname: Easwaran
mesh_terms: D000535:Aluminum / Q000737:chemistry*; D001704:Biopolymers; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D010766:Phosphorylation; D017433:Protein Structure, Secondary; D016875:tau Proteins / Q000737:chemistry*
chemical_list: D001704:Biopolymers; D016875:tau Proteins; D000535:Aluminum