Tau Protein Turnover is the continuous, regulated process of synthesis, post-translational modification, and degradation of the Tau protein within neurons. Tau is a microtubule-associated protein critical for stabilizing the internal structure and transport systems of the axon. A healthy, efficient turnover rate ensures the rapid clearance of old or hyperphosphorylated Tau, which prevents its misfolding and aggregation into neurofibrillary tangles. These tangles are a primary pathological hallmark of Alzheimer’s disease and other tauopathies. Maintaining optimal turnover is a key objective in neuroprotective strategies.
Origin
The term combines the name of the protein, Tau, derived from the Greek letter τ, with turnover, a biological term for the rate at which a substance is replaced and recycled. It is a fundamental concept in molecular neurobiology. The clinical relevance of Tau turnover has dramatically increased with the understanding of its direct role in age-related neurodegeneration.
Mechanism
Normal turnover is precisely regulated by a delicate balance of kinases, which phosphorylate Tau, and phosphatases, which dephosphorylate it. Hyperphosphorylation is the pathological trigger that causes Tau to detach from microtubules and aggregate into toxic oligomers and tangles. The clearance of Tau is primarily mediated by the ubiquitin-proteasome system and the autophagy-lysosome pathway. Hormones, such as estrogen, can modulate the activity of these regulatory enzymes, thereby indirectly influencing the overall Tau protein turnover rate.
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