Conformational change and GTPase activity of human tubulin: A comparative study on Alzheimer ’s disease and healthy brain

Axonal microtubule disintegration and neuronal death are characteristics of Alzheimer ’s disease. GTP‐cap which is comprised of GTP‐tubulin is highly important in microtubule dynamic instability. We proposed that in Alzheimer’s disease age‐dependent conformational changes of tubulin causing altered intrinsic tubulin GTPase activity and decreased GTP‐cap length precedes ta u detachment and its subsequent hyperphosphorylation. Human tubulin was purified from normal young adult, normal aged and Alzheimer’s brains. Prolonged lag phase, increased critical concentration and GTPase activity concurrent with profound conformational changes and contracted intermolecular MT‐ tau distances were found in Alzheimer’ brains compared with normal young and aged ones. AbstractIn Alzheimer's disease (AD), the most common form of dementia, microtubules (MTs) play a pivotal role through their highly dynamic structure and instability. They mediate axonal transport that is crucial to synaptic viability. MT assembly, dynamic instability and stabilization are modulated by tau proteins, whose detachment initiates MT disintegration. Albeit extensive research, the role of GTPase activity in molecular mechanism of stability remains controversial. We hypothesized that GTPase activity is altered in AD leading to microtubule dynamic dysfunction and ultimately to neuronal death. In this paper, fresh tubulin was purified by chromatography from normal young adult, normal aged, and Alzheimer's...

Source: Journal of Neurochemistry - April 12, 2020 Category: Neuroscience Authors: Shima Rajaei, Saeed Karima, Hessam Sepasi Tehrani, Somayeh Shateri, Somayeh Mahmoodi Baram, Meisam Mahdavi, Farzad Mokhtari, Alimohammad Alimohammadi, Abbas Tafakhori, Abolfazl Amiri, Vajiheh Aghamollaii, Hamid Fatemi, Masoumeh Rajabibazl, Fa Tags: ORIGINAL ARTICLE Source Type: research