Tau dysregulation, a key mediator of neurodegeneration, has stimulated the development of therapeutics for the treatment of AD and non-AD tauopathies. Given these treatments are currently being developed, a non-invasive method of determining the tau burden in the brain would allow a better understanding of the pathophysiology of AD, FTLD and other tau-related neurodegenerative conditions.
An overview of Tau
Tau protein is a low molecular weight microtubule-related protein (MAP), which is a highly asymmetrical phosphoprotein, mainly distributed in the central nervous system. Tau protein does not have any regular secondary structure (such as exposed - helix or helix - lamellar structure), and the most prominent feature of its primary structure is that it has 3 to 4 repetitive regions containing 31 or 32 amino acid residues at the carboxyl terminus of the protein. The main structure presents the "repeat series" of Pro-Gly-Gly-Gly. These repetitive areas are the tubule-binding areas that make up the Tau protein. Tau protein is mainly distributed in the brain's frontal lobe, hippocampus, neurons in the inner olfactory region and the axon of peripheral nerves, and its binding force with the axon is stronger than that with the cell body or dendrites.
Major types of Tau
Normal Tau protein can be divided into two kinds, one is in the central nervous system (molecular weight 4500~6000), known as low molecular weight Tau (LMW-Tau). The other is found in the peripheral nervous system (about 9000 molecular weight) and is called high molecular weight Tau(HMW-Tau). Tau proteins are encoded by genes located on the long arm of chromosome 17. Because of the differences in mRNA of transcription products during post-transcriptional shearing and modification, 6 isomers can be formed, which are named Tau1~Tau6 respectively. They differ in the carboxyl terminal of 3R(3R-Tau) or 4R(4R-Tau). The six Tau isomers can be divided into three types: soluble non-abnormal phosphorylation of Tau (C-tau), soluble abnormal phosphorylation of Tau (AD p-tau), and insoluble aggregation of Tau (PHF-tau) with double helix.
Antagonist of Tau
As the abnormal modification of Tau protein involves a variety of enzymes, its antagonists are various. Most of them are phosphatases and activator drugs to reduce the phosphorylation of Tau protein. There are also some antagonists that limit the abnormal glycosylation of the Tau protein using a specific glycosidase that breaks down the glycosylation.
Tau and diseases
Tau protein is a kind of neuronal microtubule sequestrated cytoskeleton protein. Abnormal phosphorylation of Tau protein is an important factor leading to intracellular nerve fiber tangles, which can cause transportation, storage and release obstacles of related neurotransmitters and cause learning and memory impairment. Large numbers of neuronal tangles are also associated with neuronal death and cognitive decline. In addition, a large number of abnormal modified Tau proteins exist in the brain of patients with Alzheimer's disease (AD) , which play an important role in the pathogenesis of AD.
1. Goedert, M., & Spillantini, M. G. (2011). Pathogenesis of the tauopathies. Journal of Molecular Neuroscience, 45 (3), 425.
2. Martin, L., Latypova, X., & Terro, F. (2011). Post-translational modifications of tau protein: implications for Alzheimer's disease. Neurochemistry international, 58 (4), 458-471.