About this Research Topic
Tauopathies are characterized by the aberrant modification, splicing, and aggregation of the microtubule-associated protein Tau into filamentous inclusions in neurons and glia. Tau pathology is present across a wide spectrum of neurodegenerative diseases including Alzheimer's disease, fronto-temporal dementias, Pick's disease, progressive supranuclear palsy, chronic traumatic encephalopathy, Huntington's and Parkinson's diseases, among others. Given the combined prevalence of these diseases and the importance of Tau pathology in Alzheimer's disease, research on tauopathy should be considered a priority.
Although great advances have been made thus far, a number of unsolved questions remain regarding the molecular and cellular mechanisms by which Tau pathology (in the presence or absence of tau mutations) is initiated, amplified and propagated; and how it evolves into the diverse features of tauopathy culminating in dementia and brain shrinkage. In addition, while a number of studies indicated that early cognitive deficits are driven by synaptic dysfunction and deficits in neuritic connectivity, the underlying mechanisms and how they lead to clinical symptoms are not fully understood; a topic of great relevance in the human context. Investigations on these aspects will expand our knowledge on the pathways involved and should provide biomarkers of evolving Tau pathology as well as enable the development of much needed therapies targeting Tau. So far, attempts with inhibitors of kinase activity or tau aggregation, or with compounds aiming at increasing microtubule stability produced disappointing results due to high toxicity or lack of efficacy. Similarly, although preclinical studies suggested great potential for tau immunotherapies, an increasing number of clinical trials based on anti-tau antibodies are halted at phase 2.
This Research Topic in Frontiers in Neurology will focus mainly on the recent developments on Tau pathology in Alzheimer's disease, however other CNS diseases with tauopathy will be discussed as represented by animal models and human studies. The scope of this Research Topic includes, but is not limited to: i) Tau pathological conformation and aggregation in Alzheimer's and other pathologies; ii) Tau-mediated myelin vacuolization; iii) Tau-dependent vascular pathology; iv) the link between Tau pathology, oxidative stress and neuroinflammation; v) the interrelation between Tau and amyloid pathology; vi) Tau propagation and cell interactions; vii) molecular basis of the differential vulnerability of different brain regions to Tau pathology; viii) how a greater insight into Tau pathology can then be translated into the clinic. In this Research Topic, we welcome the contribution of Original Research articles as well as Reviews on the subject.
Keywords: Tau pathology, tauopathy, Alzheimer’s disease, neurodegeneration, dementia, tau therapeutics, animal models
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