The authors would like to thank Alzheimer's Research UK (Grant refs: ARUK-PPG2014A-21 and ARUK-NSG2015-1 to BP and DK) who have provided support for relevant projects leading to this review.Peer reviewedPostprin

Koss, David J

Platt, Bettina

Behavioural Pharmacology

English

The authors would like to thank Alzheimer's Research UK (Grant refs: ARUK-PPG2014A-21 and ARUK-NSG2015-1 to BP and DK) who have provided support for relevant projects leading to this review.Peer reviewe

The Open University

Alzheimer's disease pathology and the unfolded protein response : Prospective pathways and therapeutic targets

David J. Koss

Bettina Platt

Crossref

Alzheimer’s disease pathology and the unfolded protein response: prospective pathways and therapeutic targets

Many vital interdependent cellular functions including proteostasis, lipogenesis and Ca2+ homeostasis are executed by the endoplasmic reticulum (ER). Exogenous insults can impair ER performance: this must be rapidly corrected or cell death will ensue. Protective adaptations can boost the functional capacity of the ER and form the basis of the unfolded protein response (UPR). Activated in response to the accumulation of misfolded proteins, the UPR can halt protein translation while increasing protein-handling chaperones and the degradation of erroneous proteins through a conserved three-tier molecular cascade. However, prolonged activation of the UPR can result in the maladaptation of the system, resulting in the activation of inflammatory and apoptotic effectors. Recently, UPR and its involvement in neurodegenerative disease has attracted much interest and numerous potentially 'drugable' points of crosstalk are now emerging. Here, we summarize the functions of the ER and UPR, and highlight evidence for its potential role in the pathogenesis of Alzheimer's disease, before discussing several key targets with therapeutic potential.</p

Koss, David J.

Discovery Research Portal

Alzheimer's disease pathology and the unfolded protein response:Prospective pathways and therapeutic targets

https://aura.abdn.ac.uk/bitstream/2164/10126/1/BP_17_20_R1_1_.pdf

Alzheimer's disease pathology and the unfolded protein response : Prospective pathways and therapeutic targets

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The Open University

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Discovery Research Portal

Discovery Research Portal