PERK inhibition as a therapeutic strategy for Alzheimer disease

 

The overall objective of this proposal is to determine the impact of PERK inhibition on the UPR, tau pathology, brain structure, and synaptic integrity using manganese-enhanced (ME-MRI) in a tauopathic mouse model of Alzheimer’s disease (AD). Project 1 will determine the impact of PERK inhibition on tau pathology and UPR markers in rTg4510 mice. Project 2 will determine the effect of PERK inhibition on brain atrophy (volumetric T2 MRI) and synaptic integrity (ME-MRI) in rTg4510 mice.

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pTau reduction in rTg4510 mice in an acute GSK2606414/new compound treatment paradigm

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The overall objective of this proposal is to determine the earliest time point at which GSK2606414 reduces pathological tau species in a transgenic mouse model of accelerated tauopathy akin to Alzheimer’s and 25 other disorders.