Replies to post #136239 on Biotech Values

[biomaven0]

>tau

FWIW, in an animal model, sodium selenate (a form of selenium available as an OTC supplement) seems to abrogate tau pathology:

Sodium selenate mitigates tau pathology, neurodegeneration, and functional deficits in Alzheimer's disease models
Janet van Eersela,b, Yazi D. Kea, Xin Liua, Fabien Deleruea, Jillian J. Krilb, Jürgen Götza,1, and Lars M. Ittnera,1
+ Author Affiliations

aAlzheimer's and Parkinson's Disease Laboratory, Brain and Mind Research Institute, University of Sydney, Camperdown, New South Wales 2050, Australia; and
bDepartment of Pathology, University of Sydney, Camperdown, New South Wales 2016, Australia
Communicated by Etienne-Emile Baulieu, Institut National de la Sante et de la Recherche Médicale, Le Kremlin-Bicetre, France, June 25, 2010 (received for review June 7, 2010)

Abstract

Alzheimer's disease (AD) brains are characterized by amyloid-ß-containing plaques and hyperphosphorylated tau-containing neurofibrillary tangles (NFTs); however, in frontotemporal dementia, the tau pathology manifests in the absence of overt amyloid-ß plaques. Therapeutic strategies so far have primarily been targeting amyloid-ß, although those targeting tau are only slowly beginning to emerge. Here, we identify sodium selenate as a compound that reduces tau phosphorylation both in vitro and in vivo. Importantly, chronic oral treatment of two independent tau transgenic mouse strains with NFT pathology, P301L mutant pR5 and K369I mutant K3 mice, reduces tau hyperphosphorylation and completely abrogates NFT formation. Furthermore, treatment improves contextual memory and motor performance, and prevents neurodegeneration. As hyperphosphorylation of tau precedes NFT formation, the effect of selenate on tau phosphorylation was assessed in more detail, a process regulated by both kinases and phosphatases. A major phosphatase implicated in tau dephosphorylation is the serine/threonine-specific protein phosphatase 2A (PP2A) that is reduced in both levels and activity in the AD brain. We found that selenate stabilizes PP2A-tau complexes. Moreover, there was an absence of therapeutic effects in sodium selenate-treated tau transgenic mice that coexpress a dominant-negative mutant form of PP2A, suggesting a mediating role for PP2A. Taken together, sodium selenate mitigates tau pathology in several AD models, making it a promising lead compound for tau-targeted treatments of AD and related dementias.

http://www.pnas.org/content/early/2010/07/13/1009038107

[Kadaicher1]

Dew, I doubt that tau theory for a few reasons. Firstly it appears that tau is used to transport metals to the edge of the cells for removal, and lack of tau appears to cause buildup of iron in the SN leading to Parkinsons. Secondly is that prions, first suspected back in the 80's have recently been identified in the process and may be the infectious component.
http://www.pnas.org/content/109/5/1737
[Aß neurotoxicity depends on interactions between copper ions, prion protein, and N-methyl-d-aspartate receptors
Haitao Youa,1, Shigeki Tsutsuib,1, Shahid Hameeda, Thomas J. Kannanayakalb, Lina Chena, Peng Xiac, Jordan D. T. Engbersa, Stuart A. Liptonc, Peter K. Stysb,2, and Gerald W. Zamponia,2
+ Author Affiliations

aDepartment of Physiology and Pharmacology and
bDepartment of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada, T2N 4N1; and
cDel E. Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037
Edited* by Stanley B. Prusiner, University of California, San Francisco, CA, and approved December 21, 2011 (received for review July 5, 2011)

Abstract
N-methyl-d-aspartate receptors (NMDARs) mediate critical CNS functions, whereas excessive activity contributes to neuronal damage. At physiological glycine concentrations, NMDAR currents recorded from cultured rodent hippocampal neurons exhibited strong desensitization in the continued presence of NMDA, thus protecting neurons from calcium overload. Reducing copper availability by specific chelators (bathocuproine disulfonate, cuprizone) induced nondesensitizing NMDAR currents even at physiologically low glycine concentrations. This effect was mimicked by, and was not additive with, genetic ablation of cellular prion protein (PrPC), a key copper-binding protein in the CNS. Acute ablation of PrPC by enzymatically cleaving its cell-surface GPI anchor yielded similar effects. Biochemical studies and electrophysiological measurements revealed that PrPC interacts with the NMDAR complex in a copper-dependent manner to allosterically reduce glycine affinity for the receptor. Synthetic human Aß1–42 (10 nM–5 µM) produced an identical effect that could be mitigated by addition of excess copper ions or NMDAR blockers. Taken together, Aß1–42, copper chelators, or PrPC inactivation all enhance the activity of glycine at the NMDAR, giving rise to pathologically large nondesensitizing steady-state NMDAR currents and neurotoxicity. We propose a physiological role for PrPC, one that limits excessive NMDAR activity that might otherwise promote neuronal damage. In addition, we provide a unifying molecular mechanism whereby toxic species of Aß1–42 might mediate neuronal and synaptic injury, at least in part, by disrupting the normal copper-mediated, PrPC-dependent inhibition of excessive activity of this highly calcium-permeable glutamate receptor.]

Note that abstract has been edited by Stanley Prusiner. who won the Nobel for his prion discovery work.
My lay opinion is that part of the answer will be about protecting tau, rather than stopping it.

[genisi]

Tau pathology spread in AD

The idea isn't new. One group showed evidence in-vitro and wrote: "We hypothesize that extracellular Tau aggregates can transmit a misfolded state from the outside to the inside of a cell, similar to prions."

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2676015/?tool=pubmed

And these groups showed the spread of tauopathy from cell to cell in the brains of tau transgenic mice by injecting brain samples in two mice strains:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726961/?tool=pubmed