Tau (CP-13) | ALZFORUM
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).
Active Tau Vaccine: Hints of Slowing Neurodegeneration
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.
Tau, Speckle Wrecker, Disrupts the Nuclear Home - ALZFORUM
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).
Tau (PHF-1) | ALZFORUM
2024年2月5日 · Site-directed mutagenesis of recombinant tau reinforced this finding: Replacement of either serine-396 or serine-404 with an alanine residue, which cannot be phosphorylated, largely eliminated PHF-1 reactivity with tau on western blots (Otvos et al., 1994; Strang et al., 2017). PHF-1 reacts with tau phosphorylated at serine-396 and serine-404.
Tau Modification Drugs Take a Hit with Negative Trial
2024年11月14日 · The rationale behind small-molecule OGA inhibition is that these drugs will decrease tau hyperphosphorylation and aggregation into neurofibrillary tangles (right). [Courtesy of Eli Lilly & Co.] In his October 30 CTAD presentation, Lilly’s Adam Fleisher showed that ceperognastat missed its secondary outcome of reducing clinical symptoms in ...
Chimeric Protein Dephosphorylates Tau, Improves Memory
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.
Widely Used Tau Seeding Assay Challenged - ALZFORUM
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.
THY-Tau22 - ALZFORUM
2019年11月25日 · THY-Tau22 mice are a model for tau aggregation, a pathological hallmark of Alzheimer's disease as well as numerous tauopathies. With age these mice develop a variety of tau-related neuropathological changes, including tau hyperphosphorylation, neurofibrillary-like tau inclusions, and ghost tangles.
rTg(tauP301L)4510 - ALZFORUM
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 ...
Acetylation Accelerates Aggregation of 3R, but Not 4R, Tau
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.