2024年2月7日 · CP-13 immunotherapy has been tested in disease models, with limited success. Passive immunization of JNPL3 mice, which express human tau with the P301L mutation, prevented the appearance of pathological forms of tau, although this effect depended upon the brain region and tau fraction examined (d’Abramo et al., 2015).

2020年5月22日 · Unlabeled tau fragments aggregated readily, while C-terminally tagged tau formed only a third as many aggregates, and N-terminally tagged tau formed none. Electron microscopy revealed that C-terminally labeled tau aggregated into short fibrils, about twice as thick as those generated by unlabeled tau, with a distinct appearance from PHFs.

2020年4月15日 · Met11-tau potentiated tau pathology more potently than did full-length tau, boosting the number of hippocampal neurons containing tau-positive inclusions by about 50 percent. This confirmed its toxicity. The researchers then generated an antibody to Met11 tau, and injected 10 mg/kg into Thy-Tau22 mice seven times over the course of five months.

2021年2月2日 · As originally described, the hemizygous animals express human tau at levels comparable to endogenous murine tau, whereas homozygotes express human tau at approximately twice endogenous levels. Transgene expression was strongest in the cerebellum and hippocampus, followed by the thalamus, hypothalamus, spindal cord, brainstem and cortex.

2024年2月7日 · Consistent with the hypothesis that tau adopts the Alz-50 conformation under conditions of oxidative stress, in one study, all Alz-50-immunoreactive neurons in AD brains also stained for the antioxidant heme oxygenase-1 (Takeda et al., 2000). Post-translational modifications of tau increase Alz-50 immunoreactivity.

2014年12月22日 · T2 mice were then crossed with the CaMKIIα-tTA activator line to create bi-transgenic mice (designated rT2/T2 when homozygous for the MAPT P301L transgene). rT2/T2 mice express even more tau P301L than rTg4510 mice, yet neurodegeneration is delayed and tau pathology occurs later and is less extreme in rT2/T2 mice than in rTg4510 mice. These ...

2021年4月16日 · Tau Meets Speckle. In HEK cells expressing wild-type tau (top), no tau aggregates (green) form, and the speckle protein SRRM2 (red) stays in the nucleus (blue). In cells expressing P301S tau (bottom), tau aggregates form in the nucleus and cytoplasm (black background). Aggregates co-localize with SRRM2 in both locales (1 and 2, bottom right).

2024年10月6日 · They generated a chimeric protein, D20, that selectively recruits protein phosphatase 1 (PP1) to tau. PP1 then snips off phospho groups at several AD-related sites. In two tauopathy mouse models, peripheral administration of D20 lowered p-tau and total tau in the brain. Chronic dosing with D20 restored synaptic density and memory to normal.

2023年10月6日 · Four-R tau formed three times as many fibrils as did 3R tau after five days. Acetylation accelerated 3R tau aggregation, with ThT fluorescence being detectable after 1.5 days (image above). The scientists think that, by capping the positively charged lysines, acetylation removes electrostatic repulsion, driving 3R fibril formation.

2018年10月22日 · Tau antibody CBTAU-24.1 binds to proline-rich region P2, just before the four repeat domains. [Courtesy of Zhang et al., Structure.] Janssen researchers previously exposed pooled memory B cells taken from healthy donors to phosphorylated tau, and recovered 52 different tau-binding antibodies (Pascual et al., 2017). CBTAU-24.1 was one of them.