Four-repeat tauopathies
Autor: | Wassilios G. Meissner, Victor L. Villemagne, Gesine Respondek, Kerstin Schweyer, Günter U. Höglinger, Franziska Hopfner, Thomas Koeglsperger, Matthias Höllerhage, Ulrich Müller, Amir Tayaranian Marvian, Osama Sabri, Matthias Brendel, Gabor G. Kovacs, Niko-Petteri Nykänen, Sigrid C. Schwarz, Thomas W. Rösler, Johannes Levin, Henryk Barthel |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Microtubule-associated protein Tau protein tau Proteins Disease Protein degradation Progressive supranuclear palsy methods [Neuropathology] 03 medical and health sciences 0302 clinical medicine Alzheimer Disease medicine Humans Corticobasal degeneration ddc:610 Neuropathology Neurons biology General Neuroscience Brain medicine.disease metabolism [tau Proteins] 030104 developmental biology Tauopathies metabolism [Brain] metabolism [Neurons] biology.protein Tauopathy metabolism [Tauopathies] Alzheimer's disease Neuroscience metabolism [Alzheimer Disease] 030217 neurology & neurosurgery |
Zdroj: | Progress in neurobiology 180, 101644 (2019). doi:10.1016/j.pneurobio.2019.101644 |
ISSN: | 0301-0082 |
Popis: | Tau is a microtubule-associated protein with versatile functions in the dynamic assembly of the neuronal cytoskeleton. Four-repeat (4R-) tauopathies are a group of neurodegenerative diseases defined by cytoplasmic inclusions predominantly composed of tau protein isoforms with four microtubule-binding domains. Progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease or glial globular tauopathy belong to the group of 4R-tauopathies. The present review provides an introduction in the current concept of 4R-tauopathies, including an overview of the neuropathological and clinical spectrum of these diseases. It describes the genetic and environmental etiological factors, as well as the contemporary knowledge about the pathophysiological mechanisms, including post-translational modifications, aggregation and fragmentation of tau, as well as the role of protein degradation mechanisms. Furthermore, current theories about disease propagation are discussed, involving different extracellular tau species and their cellular release and uptake mechanisms. Finally, molecular diagnostic tools for 4R-tauopathies, including tau-PET and fluid biomarkers, and investigational therapeutic strategies are presented. In summary, we report on 4R-tauopathies as overarching disease concept based on a shared pathophysiological concept, and highlight the challenges and opportunities on the way towards a causal therapy. |
Databáze: | OpenAIRE |
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