The Fox news article here;
http://www.foxnews.com/health/2013/10/10/scientists-stop-brain-cells-in-mice-from-dying-in-potential-alzheimer-treatment/
The abstract here;
Oral Treatment Targeting the Unfolded Protein Response Prevents Neurodegeneration and Clinical Disease in Prion-Infected Mice
- Julie A. Moreno1,
- Mark Halliday1,
- Colin Molloy1,
- Helois Radford1,
- Nicholas Verity1,
- Jeffrey M. Axten2,
- Catharine A. Ortori3,
- Anne E. Willis1,
- Peter M. Fischer4,
- David A. Barrett3 and
- Giovanna R. Mallucci1,*
+ Author Affiliations
- ↵*Corresponding author. E-mail: grm7@le.ac.uk
Abstract
During prion disease, an increase in
misfolded prion protein (PrP) generated by prion replication leads to
sustained overactivation
of the branch of the unfolded protein response
(UPR) that controls the initiation of protein synthesis. This results in
persistent
repression of translation, resulting in the loss
of critical proteins that leads to synaptic failure and neuronal death.
We
have previously reported that localized genetic
manipulation of this pathway rescues shutdown of translation and
prevents
neurodegeneration in a mouse model of prion
disease, suggesting that pharmacological inhibition of this pathway
might be of
therapeutic benefit. We show that oral treatment
with a specific inhibitor of the kinase PERK (protein kinase RNA–like
endoplasmic
reticulum kinase), a key mediator of this UPR
pathway, prevented UPR-mediated translational repression and abrogated
development
of clinical prion disease in mice, with
neuroprotection observed throughout the mouse brain. This was the case
for animals
treated both at the preclinical stage and also
later in disease when behavioral signs had emerged. Critically, the
compound
acts downstream and independently of the primary
pathogenic process of prion replication and is effective despite
continuing
accumulation of misfolded PrP. These data
suggest that PERK, and other members of this pathway, may be new
therapeutic targets
for developing drugs against prion disease or
other neurodegenerative diseases where the UPR has been implicated.
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