Tauopathies: new perspectives and challenges

Abstract

Background Tauopathies are a class of neurodegenerative disorders characterized by neuronal and/or glial tau-positive inclusions. Main body Clinically, tauopathies can present with a range of phenotypes that include cognitive/behavioral-disorders, movement disorders, language disorders and non-specific amnestic symptoms in advanced age. Pathologically, tauopathies can be classified based on the predominant tau isoforms that are present in the inclusion bodies (i.e., 3R, 4R or equal 3R:4R ratio). Imaging, cerebrospinal fluid (CSF) and blood-based tau biomarkers have the potential to be used as a routine diagnostic strategy and in the evaluation of patients with tauopathies. As tauopathies are strongly linked neuropathologically and genetically to tau protein abnormalities, there is a growing interest in pursuing of tau-directed therapeutics for the disorders. Here we synthesize emerging lessons on tauopathies from clinical, pathological, genetic, and experimental studies toward a unified concept of these disorders that may accelerate the therapeutics. Conclusions Since tauopathies are still untreatable diseases, efforts have been made to depict clinical and pathological characteristics, identify biomarkers, elucidate underlying pathogenesis to achieve early diagnosis and develop disease-modifying therapies.

MicroRNA Networks in Cognition and Dementia

“…In an effort to study gene networks of human disease, mice models have been used to provide a cross-species network approach to drug discovery. The mice studied were F1 offspring crossed with TPR50 mice that expressed the human Tau transgene, as tauopathies are an established class of dementia and other neurodegenerative diseases [ 47 , 57 , 96 ]. The miRNA profiles from the mice were compared to proteomic and transcriptomic data from the human brain to close the species gap.…”

“…As with Aβ, accumulation of abnormal tau aggregates is a classic pathological feature in dementia-related diseases such as AD. Notably, growing evidence supports independent as well as synergistic mechanisms between Aβ and tau [ 3 , 96 , 99 ]. Aberrant tau hyperphosphorylation and aggregate formation in AD is reportedly mediated by miRNA networks, as supported by a new report on miR-23b-3p.…”

A Glimpse of Molecular Biomarkers in Huntington’s Disease

“…Tau is primarily expressed in the axon of neurons and is involved in microtubule assembly and stabilization, neurite outgrowth and synaptic plasticity [ 49 ]. Phosphorylation and dephosphorylation are key mechanisms to regulate tau activities; they are disrupted in AD and tauopathies [ 50 , 51 ], leading to hyperphosphorylation of tau, destabilization of microtubules and formation of fibrils and aggregates that contribute to cellular dysfunction and death [ 51 , 52 , 53 , 54 ]. From the first reports indicating alterations of tau in the brains of HD patients [ 55 , 56 ], there is appealing evidence of tau hyperphosphorylation, increased total levels, mis-splicing affecting the 4R-Tau/3R-Tau ratio, protein misfolding and aggregation, subcellular redistribution, neurofibrillary tangles and neuropil threads in the brains of HD patients [ 57 , 58 ] that appears to correlate with late cognitive deficits and dementia in HD patients [ 56 , 59 ], suggesting that HD may have a tauopathy component [ 60 ] that deserves further exploration.…”

Curcumin Scaffold as a Multifunctional Tool for Alzheimer’s Disease Research

“…Studies show that the total amount of tau proteins in AD brains is increased significantly, and the increased tau proteins are usually in the form of excessive abnormal phosphorylation, which means that if the tau protein is abnormally phosphorylated, it is easy to form paired helical filaments (PHF), which can lead to neurofibrillary tangles (NFTs). NFTs are highly related to the occurrence of AD [22][23][24]. Clearly, developing new imaging probes that target NFTs is becoming of great significance for the accurate diagnosis of AD.…”