Asset Details
Do you wish to reserve the book?
Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases
Do you wish to request the book?
Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases
2014
Overview
Key Points
Equilibrated protein homeostasis (referred to as proteostasis) requires the dynamic coordination of efficient folding of newly synthesized proteins, quality control and degradative mechanisms to reduce the load of unfolded and/or misfolded proteins and thereby prevent abnormal protein aggregation. In response to proteostasis perturbations, the folding and/or degrading capacity of the endoplasmic reticulum (ER) is dynamically adjusted by the induction of a complex signalling network known as the unfolded protein response (UPR).
Most neurodegenerative diseases are considered to be protein misfolding disorders. They have distinct clinical manifestations, but they all involve the accumulation of abnormally folded proteins in the form of small oligomers, aggregates or large-protein inclusions. Disturbance of several aspects of proteostasis contributes to the progression of these neurodegenerative diseases.
Perturbation of ER function or the UPR may be part of the aetiology of several diseases; that is, disease proteins may directly or indirectly perturb the UPR machinery and alter the function of the secretory pathway at different levels, resulting in irreversible alterations in neuronal proteostasis and degeneration.
UPR activation can either enhance or reduce neurodegeneration. UPR adaptive responses or pro-apoptotic programmes are possibly triggered depending on the load of misfolded proteins and the specific UPR signalling mechanisms that are activated.
An ER adaptive response can engage a preconditioning stage by adjusting proteostasis in neurons but can also propagate cell-non-autonomously in the whole organism to maintain global proteostasis and limit ageing. Physiological perturbation of the ER through the engagement of adaptive ER-hormetic mechanisms could be exploited to develop therapeutic strategies that attenuate neurodegeneration.
UPR pathways have physiological functions in different aspects of brain development and function, such as CNS development, learning, memory and hypothalamic functions.
The unfolded protein response (UPR) is a homeostatic mechanism by which cells regulate levels of misfolded proteins in the endoplasmic reticulum (ER). Here, Hetz and Mollereau provide an overview of the most recent findings addressing the relevance of ER stress in the nervous system.
The unfolded protein response (UPR) is a homeostatic mechanism by which cells regulate levels of misfolded proteins in the endoplasmic reticulum (ER). Although it is well characterized in non-neuronal cells, a proliferation of papers over the past few years has revealed a key role for the UPR in normal neuronal function and as an important driver of neurodegenerative diseases. A complex scenario is emerging in which distinct UPR signalling modules have specific and even opposite effects on neurodegeneration depending on the disease context. Here, we provide an overview of the most recent findings addressing the biological relevance of ER stress in the nervous system.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/106
/ 13/51
/ 13/56
/ 13/95
/ 14/1
/ 14/10
/ 14/19
/ 14/34
/ 14/35
/ 14/5
/ 14/56
/ 14/63
/ 14/69
/ 82/79
/ 82/80
/ 82/81
/ 82/83
/ 96/63
/ 96/95
/ 96/98
/ Animal Genetics and Genomics
/ Animals
/ Disease
/ Endoplasmic Reticulum - physiology
/ Humans
/ Neurodegenerative Diseases - physiopathology
/ Stress
