Tau proteins are a family of microtubule-associated proteins predominantly expressed in neurons, where their primary physiological role is to stabilize the internal structure of axons and regulate axonal transport. In a pathological state, these proteins become excessively hyperphosphorylated and aggregate into insoluble neurofibrillary tangles, which is a hallmark pathology of several progressive neurodegenerative disorders, collectively known as tauopathies, including Alzheimer’s disease. The accumulation of these toxic aggregates disrupts neuronal transport and signaling, leading to widespread cellular dysfunction.
Origin
Tau proteins were first identified as factors promoting microtubule assembly in the brain and were named for their association with these structures. Their clinical significance in hormonal health is an emerging area of research, recognizing that sex steroid hormones and metabolic factors, such as insulin resistance, can directly modulate the phosphorylation state and aggregation propensity of tau.
Mechanism
Under normal physiological conditions, tau is phosphorylated at a low, regulated level, allowing it to dynamically regulate microtubule stability. The pathological mechanism involves the excessive hyperphosphorylation of tau, which causes the protein to detach from the microtubules, leading to microtubule destabilization and the subsequent self-aggregation of tau into insoluble paired helical filaments. Estrogen, for instance, has been shown to have a protective effect in some preclinical models by modulating the kinases and phosphatases that control tau phosphorylation, highlighting a critical neuro-endocrine link in tauopathy risk.
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