Old and New Insights into the Role of Tau in Neurodegeneration

Dear Colleagues,

Tau is a natively unfolded microtubule-associated protein that is predominantly expressed in neurons. The cerebral accumulation of abnormal, aggregated filamentous assemblies of hyperphosphorylated tau represents a key feature in many neurodegenerative diseases which, for this reason, are grouped under the common name of tauopathies. Despite many decades of research, no effective therapy is currently available for these pathologies. In part, these challenges in treatment and diagnosis reflect our limited understanding—if any—of the specific processes driving neurodegeneration, including tau contribution.

A leading hypothesis suggests that the anatomical distribution of tau deposits, rather than the molecular identity of the protein, determines the nature of the tauopathy. However, biochemical studies indicate that both the degree of tau phosphorylation and the different protein isoforms can actively contribute to the clinical phenotype of the disease. Tau pathology has also been hypothesized to spread between synaptically connected neurons of the central nervous system through a prion-like mechanism by which pathological tau conformers seed misfolding of normal tau and/or other metastable proteins.

This Special Issue of Brain Sciences is dedicated to knowledge of the complex link between tau, tauopathies, aging, and neurodegeneration. We invite authors and research groups to submit review articles, research articles, or commentaries related to recent advances in these topics. Furthermore, we aim to investigate the prion-like properties of tau and its propagation, paying particular attention to the role of brain trauma in the onset and propagation of tau pathology. A new remarkable aspect of tau is its involvement in genetic instability, suggesting a relationship between cancer and neurodegenerative diseases. The activity of neuronal and non-neuronal tau in participating in the development of tumors and their sensitivity to chemotherapy will also be discussed.

Dr. Luisa Diomede
Dr. Luca Colnaghi
Guest Editors

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