Tau protein levels and isoform balance control cell intrinsic pathways including axonal transport and electrical activity in human derived neurons

FALZONE, TOMAS L.; HOLUBIEC MARIANA; BESSONE, IVAN FERNANDEZ; AVALE M

Washington DC

Simposio; Tau 2020; 2020

Alzheimer Association

The microtubule associated protein Tau undergoes many posttranslational modifications such as a tight developmental regulation of balanced 3R-4R tau isoform expression in adult human neurons. Tau protein dysfunction is a key step in the process leading to neurodegeneration and the imbalance, either towards 3R or 4R tau, has been closely associated with disease. While some disease hypotheses are focused on the toxic gain of function of abnormal tau aggregates, others propose that tau loss of function properties are involved in triggering neuronal death. Different studies have unlocked new functional roles for tau in neuronal homeostasis that range from the regulation of axonal transport dynamics to the modulation of neuron electrical properties. However, little is known on how tau isoform balance or tau protein levels are involved in the control of these critical cellular functions. Moreover, these propositions need the development of novel human 3D neural tissue to test the effect of tau modulation in the formation of pathology.