An impedimetric microelectrode-based array sensor for label-free detection of tau hyperphosphorylation in human cells.
Tauopathies such as Alzheimer's disease (AD) belong to the group of neurodegenerative diseases that are characterised by hyperphosphorylation of the protein tau. Hyperphosphorylation of tau is one of the salient events leading to neuronal cytotoxicity and cognitive impairments. In this context, inhibition of tau hyperphosphorylation by specific tau kinase inhibitors can provide an excellent drug target for the treatment of AD and other tau-related neurodegenerative diseases. To improve the identification, optimisation and validation during the high-cost hit-to-lead cycle of AD drugs, we established a fast and sensitive label-free technique for testing the efficacy of tau kinase inhibitors in vitro. Here, we report for the first time that microelectrode-based impedance spectroscopy can be used to detect the pathological risk potential of hyperphosphorylated tau in the human neuroblastoma cell line SH-SY5Y. Our findings provide a novel real-time recording technique for testing the efficiency of tau kinase inhibitors or other lead structures directed to tau hyperphosphorylation on differentiated SH-SY5Y cells.
Jahnke
Heinz-Georg
HG
Centre for Biotechnology and Biomedicine (BBZ), University of Leipzig, Division of Molecular Biological-Biochemical Processing Technology, Deutscher Platz 5, 04103, Leipzig, Germany.
Rothermel
Andrée
A
Sternberger
Ina
I
Mack
Till G A
TG
Kurz
Randy G
RG
Pänke
Oliver
O
Striggow
Frank
F
Robitzki
Andrea A
AA
D000704:Analysis of Variance; D002227:Carbazoles; D045744:Cell Line, Tumor; D017097:Electric Impedance; D004791:Enzyme Inhibitors; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007797:Laminin; D046208:Microchip Analytical Procedures / Q000379:methods*; D008839:Microelectrodes; D009447:Neuroblastoma; D019319:Okadaic Acid; D010766:Phosphorylation; D019311:Staurosporine; D016875:tau Proteins / Q000378:metabolism*
D002227:Carbazoles; D004791:Enzyme Inhibitors; D007797:Laminin; C054369:MAPT protein, human; C512359:SRN 003-556; D016875:tau Proteins; D019319:Okadaic Acid; D038362:Glycogen Synthase Kinase 3; C080888:tau-protein kinase; D019311:Staurosporine