Methylene blue neuroprotection study

[Swarfmaker]

Besides being clunky and slow, another feature of Google Groups I
don't like is that after 60 days, you can't reply to an old post!

Phenothiazine-mediated rescue of cognition in tau transgenic mice
requires neuroprotection and reduced soluble tau burden

It has traditionally been thought that the pathological accumulation
of tau in Alzheimer's disease and other tauopathies facilitates
neurodegeneration, which in turn leads to cognitive impairment.
However, recent evidence suggests that tau tangles are not the entity
responsible for memory loss, rather it is an intermediate tau species
that disrupts neuronal function.

Thus, efforts to discover therapeutics for tauopathies emphasize
soluble tau reductions as well as neuroprotection.

Results: Here, we found that neuroprotection alone caused by methylene
blue (MB), the parent compound of the anti-tau phenothiaziazine drug,
RemberTM, was insufficient to rescue cognition in a mouse model of the
human tauopathy, progressive supranuclear palsy (PSP) and fronto-
temporal dementia with parkinsonism linked to chromosome 17 (FTDP17):
Only when levels of soluble tau protein were concomitantly reduced by
a very high concentration of MB, was cognitive improvement observed.
Thus, neurodegeneration can be decoupled from tau accumulation, but
phenotypic improvement is only possible when soluble tau levels are
also reduced.

Conclusions: Neuroprotection alone is not sufficient to rescue tau-
induced memory loss in a transgenic mouse model.

Development of neuroprotective agents is an area of intense
investigation in the tauopathy drug discovery field. This may
ultimately be an unsuccessful approach if soluble toxic tau
intermediates are not also reduced.

Thus, MB and related compounds, despite their pleiotropic nature, may
be the proverbial "magic bullet"because they not only are
neuroprotective, but are also able to facilitate soluble tau
clearance. Moreover, this shows that neuroprotection is possible
without reducing tau levels.

This indicates that there is a definitive molecular link between tau
and cell death cascades that can be disrupted.

Author: John O'LearyQingyou LiPaul MarinecLaura BlairErin
CongdonAmelia JohnsonUmesh JinwalJohn KorenJeffrey JonesClara
KraftMelinda PetersJose AbisambraKaren DuffEdwin WeeberJason
GestwickiChad Dickey
Credits/Source: Molecular Neurodegeneration 2010
http://7thspace.com/headlines/362179/phenothiazine_mediated_rescue_of_cognition_in_tau_transgenic_mice_requires_neuroprotection_and_reduced_soluble_tau_burden_.html

PMID: 21040568 [PubMed - in process]PMCID: PMC2989315
http://www.ncbi.nlm.nih.gov/pubmed/21040568

Full text of the article:
Molecular Neurodegeneration 2010, 5:45doi:10.1186/1750-1326-5-45
http://www.molecularneurodegeneration.com/content/5/1/45

Pub Med Central: PMCID: PMC2989315
Mol Neurodegener. 2010; 5: 45.
Published online 2010 November 1. doi: 10.1186/1750-1326-5-45.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989315/?tool=pubmed