Aging has long been considered as the main risk factor for several neurodegenerative disorders including a large group of diseases known as tauopathies. Even though neurofibrillary tangles (NFTs) have been examined as the main histopathological hallmark, they do not seem to play a role as the toxic entities leading to disease. Recent studies suggest that an intermediate form of tau, prior to NFT formation, the tau oligomer, is the true toxic species. However, the mechanisms by which tau oligomers trigger neurodegeneration remain unknown. This review summarizes recent findings regarding the role of tau oligomers in disease, including release from cells, propagation from affected to unaffected brain regions, uptake into cells, and toxicity via mitochondrial dysfunction. A greater understanding of tauopathies may lead to future advancements in regards to prevention and treatment.
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http://dx.doi.org/10.3389/fnagi.2017.00083 | DOI Listing |
Adv Protein Chem Struct Biol
January 2025
Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences Hospital (NIMHANS), Institute of National Importance, Bangalore, Karnataka, India.
Tau is a well-known microtubule-associated protein and is located in the cytoplasm of neurons, which play a crucial role in Alzheimer's diseases. Due to its preferred binding to DNA sequences found in the nucleolus and pericentromeric heterochromatin, Tau has been found within the cell nucleus, where it may be a nucleic acid-associated protein. Tau has the ability to directly interact with nuclear pore complex nucleoporins, influencing both their structural and functional integrity.
View Article and Find Full Text PDFJ Biomech Eng
January 2025
Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910, USA.
A criterion characterizing the combined neurotoxicity of amyloid beta and tau oligomers is suggested. A mathematical model that makes it possible to calculate a value of this criterion during senile plaque and NFT formation is proposed. Computations show that for physiologically relevant parameter values, the value of the criterion increases approximately linearly as time increases.
View Article and Find Full Text PDFAnal Chem
January 2025
College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Changchun 130012, China.
The early diagnosis of a disease relies on the reliable identification and quantitation of multiple core biomarkers in real-time point-of-care (POC) testing. To date, most of the multiplex photoelectrochemical (PEC) assays are inaccessible to home healthcare due to cumbersome steps, long testing time, and limited detection efficiency. The rapid and fast-response generation of independent photocurrent for multiple targets is still a great challenge.
View Article and Find Full Text PDFMolecular rotor-based fluorophores (RBFs) that are target-selective and sensitive to both polarity and viscosity are valuable for diverse biological applications. Here, we have designed next-generation RBFs based on the underexplored bimane fluorophore through either changing in aryl substitution or varying π-linkages between the rotatable electron donors and acceptors to produce red-shifted fluorescence emissions with large Stokes shifts. RBFs exhibit a twisted intramolecular charge transfer mechanism that enables control of polarity and viscosity sensitivity, as well as target selectivity.
View Article and Find Full Text PDFCommun Biol
January 2025
Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX, USA.
Aggregation of microtubule-associated tau protein is a distinct hallmark of several neurodegenerative disorders such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and progressive supranuclear palsy (PSP). Tau oligomers are suggested to be the primary neurotoxic species that initiate aggregation and propagate prion-like structures. Furthermore, different diseases are shown to have distinct structural characteristics of aggregated tau, denoted as polymorphs.
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