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Alzheimer's Research & Therapy

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Open Access 01-12-2017 | Review

PKR involvement in Alzheimer’s disease

Authors: Jacques Hugon, François Mouton-Liger, Julien Dumurgier, Claire Paquet

Published in: Alzheimer's Research & Therapy | Issue 1/2017

Abstract

Background

Brain lesions in Alzheimer’s disease (AD) are characterized by Aβ accumulation, neurofibrillary tangles, and synaptic and neuronal vanishing. According to the amyloid cascade hypothesis, Aβ1-42 oligomers could trigger a neurotoxic cascade with kinase activation that leads to tau phosphorylation and neurodegeneration. Detrimental pathways that are associated with kinase activation could also be linked to the triggering of direct neuronal death, the production of free radicals, and neuroinflammation.

Results

Among these kinases, PKR (eukaryotic initiation factor 2α kinase 2) is a pro-apoptotic enzyme that inhibits translation and that has been implicated in several molecular pathways that lead to AD brain lesions and disturbed memory formation. PKR accumulates in degenerating neurons and is activated by Aβ1-42 neurotoxicity. It might modulate Aβ synthesis through BACE 1 induction. PKR is increased in cerebrospinal fluid from patients with AD and mild cognitive impairment and can induce the activation of pro-inflammatory pathways leading to TNFα and IL1-β production. In addition, experimentally, PKR seems to down-regulate the molecular processes of memory consolidation. This review highlights the major findings linking PKR and abnormal brain metabolism associated with AD lesions.

Conclusions

Studying the detrimental role of PKR signaling in AD could pave the way for a neuroprotective strategy in which PKR inhibition could reduce neuronal demise and alleviate cognitive decline as well as the cumbersome burden of AD for patients.

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Title: PKR involvement in Alzheimer’s disease
Authors: Jacques Hugon
François Mouton-Liger
Julien Dumurgier
Claire Paquet
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Alzheimer's Research & Therapy / Issue 1/2017
Electronic ISSN: 1758-9193
DOI: https://doi.org/10.1186/s13195-017-0308-0

At a glance: The STEP trials

Springer Medicine

PKR involvement in Alzheimer’s disease

Abstract

Background

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Results

Conclusions

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