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Triple Trouble: New Knock-in Turbocharges Tauopathy They accumulated hyperphosphorylated tau in their brains and lost synapses by approximately 15 months of age, but they had no tau oligomers capable of seeding aggregates Such “seeds” are a hallmark of human tauopathies Recognizing the need for models with more robust pathology at a younger age, the authors engineered the new triple-knock-ins
LY3954068 | ALZFORUM LY3954068 is a small interfering RNA (siRNA) that targets expression of the microtubule-associated binding protein tau No information is available about the makeup of LY3954068
ApoE3 Christchurch Clings Tightly to Tau, Averting Tangles To find out, the scientists turned to surface plasmon resonance, a technique that quantifies molecular interactions in real time It showed that ApoE3Ch clings onto tau monomers immobilized on sensor chips approximately eight times more tightly than does wild-type ApoE3 Similarly, in neuroblastoma cells, glutathione S-transferase-labelled tau and GFP-tagged ApoE3Ch bound tightly (image at right)
Tau (CP-13) - ALZFORUM This monoclonal antibody, generated against paired helical filaments (PHFs) isolated from Alzheimer’s brains, recognizes tau phosphorylated at serine 202 Recognizes tau phosphorylated at serine 202 Immunoreactivity present in Alzheimer’s disease and other tauopathies Immunoreactivity absent in
Gosuranemab - ALZFORUM Background This is a humanized IgG4 monoclonal anti-tau antibody In April 2014, Bristol-Myers Squibb acquired iPierian, a biotechnology company that had developed IPN007, an antibody against extracellular, N-terminal fragments of tau (eTau) that were originally isolated from familial AD patient-derived pluripotent stem cells The rationale for this therapeutic approach is that eTau is
Tau (MC-1) - ALZFORUM The interaction of MC-1 with recombinant tau suggests that post-translational modifications are not required to generate the MC-1 epitope However, it remains possible that post-translational modifications influence the ability of tau to adopt or maintain the conformation seen by MC-1
HMTM - ALZFORUM Tau pathology is widely considered to be downstream of Aβ pathology and is more closely linked to cognitive deficits in Alzheimer's disease Mutations in the tau gene cause frontotemporal dementia, not Alzheimer's disease, but tau is considered a central drug target for all tauopathies, including Alzheimer's
A Tale of Two T Cells—Slowing Tau Spread, Shredding White Matter With T cells sidelined in these CD8 knockouts, tau pathology went on the offensive By 30 weeks of age, phospho-tau had spread deeper into the brain than in CD8-intact controls (image below) Michal Schwartz of the Weizmann Institute of Science in Rehovot, Israel, noted that these findings run counter to conventional thinking
Tau Modification Drugs Take a Hit with Negative Trial While anti-tau antibodies are beginning to look promising (see previous story), small molecules that modify tau proteins haven’t yet fared well in clinical trials At the 16th Clinical Trials on Alzheimer’s Disease conference, held October 29 to November 3 in Madrid, Eli Lilly’s negative trial