Review: Modulating the unfolded protein response to prevent neurodegeneration and enhance memory


Type
Article
Change log
Authors
Halliday, M 
Mallucci, GR 
Abstract

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.

Description
Keywords
memory, neurodegeneration, neurodegenerative diseases, therapeutics, unfolded protein response
Journal Title
Neuropathology and Applied Neurobiology
Conference Name
Journal ISSN
0305-1846
1365-2990
Volume Title
41
Publisher
Wiley-Blackwell
Sponsorship
MRC (MR/M501773/1)