Upregulated levels and pathological aggregation of abnormally phosphorylated Tau-protein in children with neurodevelopmental disorders

Abstract

The tubulin-associated unit (Tau) protein is an intrinsically disordered protein that plays a well-established role in promoting microtubule assembly and regulation of microtubule dynamics in neuronal axons at all stages of development. Identification of new interacting partners and different sub-cellular localizations of Tau in recent years led to the discovery of novel physiological functions in regulation of neuronal activity, neurogenesis, long-term depression, iron export and genomic integrity. In addition, Tau gene mutations, aberrant mRNA splicing and abnormal post-translational modifications, such as hyperphosphorylation, lead to formation of pathological, insoluble Tau aggregates that are a hallmark of neurodegenerative diseases, collectively known as tauopathies. Characterized by synaptic dysfunction, neuroinflammation/neuronal cell death and dementia, tauopathies are designated as a group of adult-onset neurodegenerative diseases. Recent studies summarized in this review document several neurological conditions and diseases in an early life stage with upregulated levels or even pathological aggregation of abnormally phosphorylated Tau protein. These findings suggest that Tau might play a previously underestimated role in neurodevelopmental disorders and regression in children.