Tauopathies are neurodegenerative disorders characterized by the deposition of aggregates composed of abnormal tau protein in the brain. Additionally, misfolded forms of tau can propagate from cell to cell and throughout the brain. This process is thought to lead to the templated misfolding of the native forms of tau, and thereby, to the formation of newer toxic aggregates, thereby propagating the disease. Therefore, modulation of the processes that lead to tau aggregation and spreading is of utmost importance in the fight against tauopathies. In recent years, several molecules have been developed for the modulation of tau aggregation and spreading. In this review, we discuss the processes of tau aggregation and spreading and highlight selected chemicals developed for the modulation of these processes, their usefulness, and putative mechanisms of action. Ultimately, a stronger understanding of the molecular mechanisms involved, and the properties of the substances developed to modulate them, will lead to the development of safer and better strategies for the treatment of tauopathies.
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http://dx.doi.org/10.3390/brainsci10110858 | DOI Listing |
Commun 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.
View Article and Find Full Text PDFNat Commun
January 2025
Department for NMR-based Structural Biology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
The pathological deposition of tau and amyloid-beta into insoluble amyloid fibrils are pathological hallmarks of Alzheimer's disease. Molecular chaperones are important cellular factors contributing to the regulation of tau misfolding and aggregation. Here we reveal an Hsp90-independent mechanism by which the co-chaperone p23 as well as a molecular complex formed by two co-chaperones, p23 and FKBP51, modulates tau aggregation.
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
Health Sciences Institute of China Medical University, Shenyang 110122, China. Electronic address:
Recently study has found a new form of copper-dependent death called cuproptosis, which differs from apoptosis, ferroptosis, and necrosis. The main process of cuproptosis is copper directly combined with lipid-acetylated proteins in the TCA cycle of mitochondrial response, leading to the aggregation of lipid-acetylated proteins and the loss of Fe-S cluster proteins, resulting in mitochondrial dysfunction, and eventually causing cell death. Previous studies demonstrated that an imbalance in copper homeostasis exacerbates the pathological progression of Alzheimer's disease (AD) through the induction of oxidative stress, inflammatory response, and the accumulation of Aβ deposition and tau protein hyperphosphorylation.
View Article and Find Full Text PDFJ Hazard Mater
January 2025
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610213, China.
The widespread use of antimicrobial agent triclosan (TCS) poses significant health risks to both aquatic organisms and humans. The research on its neurotoxicity and underlying mechanisms is, however, limited. Here we first conducted a 32-day exposure experiment with five TCS concentrations (10, 30, 60, 90 and 120 µg/L) to investigate its impact on overall gene expression in Rana omeimontis larvae.
View Article and Find Full Text PDFSci Signal
January 2025
Science Signaling, AAAS, Washington, DC 20005, USA.
Tau aggregates around HSV-1 in the brain, but is this pathological, part of an immune response, or both?
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