Beyond Neurons: Expanding the Biology of Tau Protein in Health, Disease and Therapeutic Innovation

Abstract: Tau is a microtubule-associated protein expressed mainly in neuronal cells where it plays an essential role in the development of neuronal structure, axonal transport and synaptic function. Recent advances in research suggest that Tau is also expressed in several non-neuronal cells and peripheral tissues, where it also helps in cellular signaling, cytoskeletal organization, and tissue homeostasis. The present study unfolds the role of Tau, beyond neuronal cells, discussing its molecular mechanisms underlying its dysfunction, including abnormal post-translational modifications, aggregation, and impaired protein clearance, which are implicated in the pathogenesis of tauopathies and other neurodegenerative disorders. Further, the review discusses the advancement of Tau biomarkers and therapeutic strategies, including gene-silencing approaches, immunotherapy, and targeted protein degradation. Collectively, this chapter provides an updated knowledge of the expanding biology of Tau and its significance as a promising diagnostic and therapeutic target. Keywords: Tau; Tauopathies; Neurodegeneration; Biomarkers; Therapeutic strategies