SH-SY5Y-derived neurons: a human neuronal model system for investigating TAU sorting and neuronal subtype-specific TAU vulnerability.

摘要: The microtubule-associated protein (MAP) TAU is mainly sorted into the axon of healthy brain neurons. Somatodendritic missorting a pathological hallmark many neurodegenerative diseases, including Alzheimer's disease (AD). Cause, consequence and (patho)physiological mechanisms sorting are understudied, in part also because lack readily available human neuronal model systems. neuroblastoma cell line SH-SY5Y widely used for studying physiology TAU-related pathology AD related tauopathies. cells can be differentiated neuron-like (SH-SY5Y-derived neurons) using various substances. This review evaluates whether SH-SY5Y-derived neurons suitable (i) investigating intracellular general, (ii) with respect to neuron subtype-specific vulnerability. (I) show pronounced axodendritic polarity, high levels axonally localized protein, expression all six isoforms phosphorylation similar brain. As highly proliferative accessible genetic engineering, stable transgene integration leading-edge genome editing feasible. (II) display features subcortical early affected allows analyzing region-specific differences physiology, context differential vulnerability pathology. However, several limitations should considered when neurons, e.g., clearly defined subtypes, or difficulty mimicking age-related tauopathy risk factors vitro. In brief, this discusses suitability (mis)sorting neuron-specific paradigms.