Neuropharmacology

QPS Austria Generates Novel Tauopathy Screening Tools: Two Stable SHSY-5Y Cell Lines Overexpressing Full Length and Truncated Tau441

Tau proteins are microtubule-associated proteins that play an important role in stabilizing the neuronal microtubule network. They are the major constituents of the intraneuronal and glial fibrillar lesions described in Alzheimer's disease and numerous other neurodegenerative disorders referred to as 'tauopathies'. These include progressive supranuclear palsy, corticobasal degeneration, and argyrophilic grain disease, as well as the inherited frontotemporal dementia and parkinsonism linked to chromosome 17.

Molecular analysis has revealed that hyperphosphorylation may be the important event leading to the tau aggregation that results in neurodegeneration and dementia. Development of new compounds capable of preventing tau hyperphosphorylation is an increasingly hot topic. Thus, reliable models that reflect tau hyperphosphorylation in human disease are needed.

Comparison of tau expression and phosphorylation levels in SHSY, SHSY-Tau and SHSY-tTau overexpressing cells has confirmed these new cell lines’ relevance to human disease. The tau phosphorylation pattern can be reliably modulated by distinct kinase inhibitors targeting CDK, JNK or GSK-3β.

In the presentation, two cellular systems are proposed to analyze the efficiency of Tau modulating compounds. Hyperphosphorylation and its modulation by kinase inhibitors known to be involved in tau phosphorylation are shown to be reliable indicators for the suitability of these two cell lines as in vitro models for tauopathies.

back
top
20 years in pharma R&D navigation