Abstract
Aggregation of tau protein is a pathological hallmark of Alzheimer’s disease and other neurodegenerative tauopathies. Inhibition of tau aggregation could provide a method for the treatment of these disorders. Methods to identify tau aggregation inhibitors (TAIs) in vitro are useful and here we describe assays for TAIs using purified recombinant tau protein fragments in a cell-free immunoassay format and a stably transfected cell model to create a more physiological environment.
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References
Buée L, Bussière T, Buée-Scherrer V et al (2000) Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Rev 33:95–130
Novak M, Kabat J, Wischik CM (1993) Molecular characterization of the minimal protease resistant tau unit of the Alzheimer’s disease paired helical filament. EMBO J 12:365–370
Wischik CM, Novak M, Thøgersen HC et al (1988) Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer’s disease. Proc Natl Acad Sci U S A 85:4506–4510
Mukaetova-Ladinska EB, Garcia-Sierra F, Hurt J et al (2000) Staging of cytoskeletal and b-amyloid changes in human isocortex reveals biphasic synaptic protein response during progression of Alzheimer’s disease. Am J Pathol 157:623–636
Arriagada PW, Growdon JH, Hedley-White ET, Hyman BT (1992) Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer’s disease. Neurology 42:631–639
Wilcock GK, Esiri MM (1982) Plaques, tangles and dementia: a quantitative study. J Neurol Sci 56:343–356
Maruyama M, Shimada H, Suhara T et al (2013) Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Neuron 79:1094–1108
Okamura N, Furumoto S, Fodero-Tavoletti MT et al (2014) Non-invasive assessment of Alzheimer’s disease neurofibrillary pathology using F-18-THK5105 PET. Brain 137:1762–1771
Wischik CM, Edwards PC, Lai RYK et al (1996) Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines. Proc Natl Acad Sci U S A 93:11213–11218
Wischik CM, Staff RT, Wischik DJ et al (2015) Tau aggregation inhibitor therapy: an exploratory phase 2 study in mild or moderate Alzheimer’s disease. J Alzheimers Dis 44:705–720
Bulic B, Pickhardt M, Mandelkow E (2013) Progress and developments in tau aggregation inhibitors for Alzheimer disease. J Med Chem 56:4135–4155
Taniguchi S, Suzuki N, Masuda M et al (2005) Inhibition of heparin-induced tau filament formation by phenothiazines, polyphenols, and porphyrins. J Biol Chem 280:7614–7623
Harrington CR, Storey JMD, Clunas S et al (2015) Cellular models of aggregation-dependent template-directed proteolysis to characterize tau aggregation inhibitors for treatment of Alzheimer’s disease. J Biol Chem 290:10862–10875
Melis V, Magbagbeolu M, Rickard JE et al (2015) Effects of oxidized and reduced forms of methylthioninium in two transgenic mouse tauopathy models. Behav Pharmacol 26:353–368
Brandt R, Kempf M, Lee G (1997) Expression and purification of tau for in vitro studies. In: Avila J, Brandt R, Kosik KS (eds) Brain microtubule associated proteins: modifications in disease. Harwood Academic Publishers, Amsterdam, pp 245–257
Matsudaira PT, Burgess DR (1978) SDS microslab linear gradient polyacrylamide gel electrophoresis. Anal Biochem 87:386–396
Novak M, Jakes R, Edwards PC et al (1991) Difference between the tau protein of Alzheimer paired helical filament core and normal tau revealed by epitope analysis of mAbs 423 and 7.51. Proc Natl Acad Sci U S A 88:5837–5841
Harrington CR, Edwards PC, Wischik CM (1990) Competitive ELISA for measurement of tau proteins in Alzheimer’s disease. J Immunol Methods 134:261–271
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Rickard, J.E., Horsley, D., Wischik, C.M., Harrington, C.R. (2017). Assays for the Screening and Characterization of Tau Aggregation Inhibitors. In: Smet-Nocca, C. (eds) Tau Protein. Methods in Molecular Biology, vol 1523. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6598-4_8
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DOI: https://doi.org/10.1007/978-1-4939-6598-4_8
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