Modulating the unfolded protein response to prevent neurodegeneration and enhance memory

M Halliday, GR Mallucci - Neuropathology and Applied …, 2015 - Wiley Online Library
M Halliday, GR Mallucci
Neuropathology and Applied Neurobiology, 2015Wiley Online Library
Recent evidence has placed the unfolded protein response (UPR) at the centre of
pathological processes leading to neurodegenerative disease. The translational repression
caused by UPR activation starves neurons of the essential proteins they need to function
and survive. Restoration of protein synthesis, via genetic or pharmacological means, is
neuroprotective in animal models, prolonging survival. This is of great interest due to the
observation of UPR activation in the post mortem brains of patients with A lzheimer's, P …
Recent evidence has placed the unfolded protein response (UPR) at the centre of pathological processes leading to neurodegenerative disease. The translational repression caused by UPR activation starves neurons of the essential proteins they need to function and survive. Restoration of protein synthesis, via genetic or pharmacological means, is neuroprotective in animal models, prolonging survival. This is of great interest due to the observation of UPR activation in the post mortem brains of patients with Alzheimer's, Parkinson's, tauopathies and prion diseases. Protein synthesis is also an essential step in the formation of new memories. Restoring translation in disease or increasing protein synthesis from basal levels has been shown to improve memory in numerous models. As neurodegenerative diseases often present with memory impairments, targeting the UPR to both provide neuroprotection and enhance memory provides an extremely exciting novel therapeutic target.
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