Aggregation, Transmission, and Toxicity of the Microtubule-Associated Protein Tau: A Complex Comprehension

Abstract

The microtubule-associated protein tau is an intrinsically disordered protein containing a few short and transient secondary structures. Tau physiologically associates with microtubules (MTs) for its stabilization and detaches from MTs to regulate its dynamics. Under pathological conditions, tau is abnormally modified, detaches from MTs, and forms protein aggregates in neuronal and glial cells. Tau protein aggregates can be found in a number of devastating neurodegenerative diseases known as “tauopathies”, such as Alzheimer’s disease (AD), frontotemporal dementia (FTD), corticobasal degeneration (CBD), etc. However, it is still unclear how the tau protein is compacted into ordered protein aggregates, and the toxicity of the aggregates is still debated. Fortunately, there has been considerable progress in the study of tau in recent years, particularly in the understanding of the intercellular transmission of pathological tau species, the structure of tau aggregates, and the conformational change events in the tau polymerization process. In this review, we summarize the concepts of tau protein aggregation and discuss the views on tau protein transmission and toxicity.

A Simple Sandwich Electrochemical Immunosensor for Rapid Detection of the Alzheimer’s Disease Biomarker Tau Protein

“…Electrochemical tests were performed using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) tests, which were included with the ZAHNER electrochemical workstation. Both EIS and CV measurements were performed in an electrochemi-cal cell, which consisted of a three-electrode system with a 2 mm gold plate electrode for the working electrode, a saturated calomel electrode for the reference electrode, a platinum electrode as the counter electrode, and 20 mL of 1 mM Fe(CN) 6 3−/4− (1:1)-PBS as a redox probe [29]. All the electrochemical tests were performed at room temperature.…”

“…This study developed an immune sandwich impedance sensor for rapid detection of tau protein, which was first modified with mAb1 on the basis of the DTSSP self-assembled monomolecular layer modified onto the surface of the gold electrode, then the tau protein was captured through the specific adsorption between the antigen and the antibody, and finally mAb2 was added to realize further amplification of the signal. Furthermore, electrochemical tests were performed using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) with Fe(CN) 6 3−/4− (1:1) as the probe [28].…”

A Novel Cre Recombinase Mouse Strain for Cell-Specific Deletion of Floxed Genes in Ribbon Synapse-Forming Retinal Neurons

“…Tau (τ) is a microtubule-associated, microtubule-binding protein [69][70][71][72]. The ROSA26-τGFP knockin (KI) mice contain a tau-GFP expression cassette [27] in the ROSA26 genomic locus that controls expression of green fluorescent protein-tagged tau protein (tau-GFP) after Cre-mediated excision of a transcriptional STOP cassette [28].…”

Sodium Dodecyl Sulfate Analogs as a Potential Molecular Biology Reagent

“…Taking tau as an example, this protein is natively unfolded and bound to microtubules, as described earlier. It undergoes post-translational modifications, including phosphorylation, which, in turn, leads to conformational changes and a series of oligomerization, eventually leading to the formation of filaments and fibrils [70]. The native proteins and their oligomers are actually more likely to be less folded than the late-stage filamentous and fibrillar structures and may present binding sites for Sarkosyl or SDS.…”