They let you post from jail?
You've have completely lost it haven't you. I now think you are just a lonely slug with no one to talk to. You got bit hard March 2014, lost your savings.
Prana Alzheimer's disease data features at world leading
Professor Rudolph Tanzi presents results from testing PBT2 in the
“Alzheimer’s in a Dish Model” at the Alzheimer’s Association International
Conference in Toronto, Canada.
MELBOURNE, July 27th 2016: Professor Rudolph Tanzi, Founding Scientist and Chief
Scientific Advisor for Prana Biotechnology, presented results obtained from testing
PBT2, Prana’s lead candidate for Huntington and Alzheimer’s diseases, at the
Alzheimer’s Association International Conference (AAIC) in Toronto, Canada on July
The presentation is entitled: “Reconstructing Alzheimer Amyloid and Tau Pathology in
3D Cell Cultures Derived from Human Stem Cells.”
In October, 2014, Professor Tanzi and his colleague Dr. Doo Yeon Kim of
Massachusetts General Hospital/Harvard Medical School reported in the
journal Nature that they successfully recreated Alzheimer’s disease pathology in an
organoid consisting of human stem-cell derived neurons grown in 3D cultures. The
landmark disease model, awarded with the Smithsonian 2015 American Ingenuity
Award, exhibited beta-amyloid plaque deposition, neurofibrillary tangles and neuronal
cell death, all major hallmarks of Alzheimer's disease. The ‘Alzheimer’s-in-a-Dish
Model’ provided the first proof of concept that beta-amyloid is sufficient to trigger
neurofibrillary tangle formation.
Since that time, the inventors have been expanding and further validating the model
for drug screening. At the AAIC 2016 meeting, Professor Tanzi reported testing results
with PBT2 in the ‘Alzheimer’s-in-a-Dish Model’. He found that treatment of the 3D
model cells with PBT2 significantly reduced levels of both phospho-tau (p-tau)
aggregates and Aβ42 fibrils when compared to controls, also visible with immuno-
staining. PBT2 also led to modest improvements in neuronal cell viability in the model.
Professor Tanzi reported that PBT2 testing in the 3D model resulted in dose-related,
statistically significant reductions in p-tau (40 to 56%) and soluble Aβ42 (31 to 51%).
PBT2 testing also resulted in statistically significant reductions in p-tau/total tau and
insoluble Aβ42 ranging from 34% to 37% and 31% to 46%, respectively.
PBT2 comes from a library of over 2,000 compounds which Prana is evaluating
separately for various indications. The 3D Alzheimer’s model adds to the body of
evidence that PBT2 significantly reduces both p-tau and Aß42.
Based on Prana’s prior pre-clinical and clinical testing and these new results, PBT2
appears to carry great potential for targeting both the proteins at the root of
Alzheimer’s; Aß42 and p-tau. p-tau also plays a role in other neurodegenerative
disorders, such as Huntington disease.
Copper Exchange and Redox Activity of a Prototypical 8-Hydroxyquinoline: Implications for Therapeutic Chelation
Mariusz Mital†‡, Izabela A. Zawisza‡, Magdalena Z. Wiloch§, Urszula E. Wawrzyniak§, Vijaya Kenche†, Wojciech Wróblewski§, Wojciech Bal‡, and Simon C. Drew*†
† Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria 3010, Australia
‡ Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw 02-106, Poland
§ Department of Microbioanalytics, Faculty of Chemistry, Warsaw University of Technology, Warsaw 00-664, Poland
Inorg. Chem., Article ASAP
Publication Date (Web): July 13, 2016
Copyright © 2016 American Chemical Society
The Cu2+-binding ligand 2-[(dimethylamino)-methyl-8-hydroxyquinoline forms the basic design of an experimental Alzheimer’s disease (AD) therapeutic. The metals hypothesis proposes that such ligands can redox-silence Cu2+ bound by β-amyloid Aβ1−x peptides. While binary CuL and CuL2 complexes are redox-silent, the most physiologically relevant Cu2+-bound species is a redox-active ternary CuL(NIm) complex. Metal transfer from the abundant, high-affinity, redox-silent Aβ4−x isoform to a redox-active form has implications for the use of such ligands as AD therapeutics.
The N-truncated β-amyloid (Aβ) isoform Aβ4–x is known to bind Cu2+ via a redox-silent ATCUN motif with a conditional Kd = 30 fM at pH 7.4. This study characterizes the Cu2+ interactions and redox activity of Aβx–16 (x = 1, 4) and 2-[(dimethylamino)-methyl-8-hydroxyquinoline, a terdentate 8-hydroxyquinoline (8HQ) with a conditional Kd(CuL) = 35 pM at pH 7.4. Metal transfer between Cu(Aβ1–16), CuL, CuL2, and ternary CuL(NImAβ) was rapid, while the corresponding equilibrium between L and Aβ4–16 occurred slowly via a metastable CuL(NImAβ) intermediate. Both CuL and CuL2 were redox-silent in the presence of ascorbate, but a CuL(NIm) complex can generate reactive oxygen species. Because the NImAβ ligand will be readily exchangeable with NIm ligands of ubiquitous protein His side chains in vivo, this class of 8HQ ligand could transfer Cu2+ from inert Cu(Aβ4–x) to redox-active CuL(NIm). These findings have implications for the use of terdentate 8HQs as therapeutic chelators to treat neurodegenerative disease.
Lithium is a first-line therapy for bipolar affective disorder. However, various adverse effects, including a Parkinson-like hand tremor, often limit its use. The understanding of the neurobiological basis of these side effects is still very limited. Nigral iron elevation is also a feature of Parkinsonian degeneration that may be related to soluble tau reduction. We found that magnetic resonance imaging T2 relaxation time changes in subjects commenced on lithium therapy were consistent with iron elevation. In mice, lithium treatment lowers brain tau levels and increases nigral and cortical iron elevation that is closely associated with neurodegeneration, cognitive loss and parkinsonian features. In neuronal cultures lithium attenuates iron efflux by lowering tau protein that traffics amyloid precursor protein to facilitate iron efflux. Thus, tau- and amyloid protein precursor-knockout mice were protected against lithium-induced iron elevation and neurotoxicity. These findings challenge the appropriateness of lithium as a potential treatment for disorders where brain iron is elevated (for example, Alzheimer’s disease), and may explain lithium-associated motor symptoms in susceptible patients.
P Lei, S Ayton, A T Appukuttan, S Moon, J A Duce, I Volitakis, R Cherny, S J Wood, M Greenough, G Berger, C Pantelis, P McGorry, A Yung, D I Finkelstein and A I Bush
"they becomes" f-in road scholar ey
so nearsighted you are- one of your many failures. Can't see what's in front of you or what is beyond, poor pawn. I'm looking forward to more excessive panic from you day to day. Cannot wait for the bash line when the pch is lifted.
time to live in the now
he- she is nervous because the brakes are about to be released.
Perhaps it's not just one person posting under this ID. No single right minded individual displays this sort of 24/7 bashing..
an approved drug for HD puts us in the single billions considering projected market, add considerations for other treatments? WOW... We are coming to the pivot point. We are essentially nothing if you believe mpac's have no place or virtually everything because we will knock down the doors for a variety of disease.
Sentiment: Strong Buy
We're in good shape here, neurology today has it posted and provides some good insights from experts including one representing Harvard.