TY - JOUR
T1 - Exploring ER stress response in cellular aging and neuroinflammation in Alzheimer's disease
AU - Uddin, Md Sahab
AU - Yu, Wing Shan
AU - Lim, Lee Wei
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/9
Y1 - 2021/9
N2 - One evident hallmark of Alzheimer's disease (AD) is the irregular accumulation of proteins due to changes in proteostasis involving endoplasmic reticulum (ER) stress. To alleviate ER stress and reinstate proteostasis, cells undergo an integrated signaling cascade called the unfolded protein response (UPR) that reduces the number of misfolded proteins and inhibits abnormal protein accumulation. Aging is associated with changes in the expression of ER chaperones and folding enzymes, leading to the impairment of proteostasis, and accumulation of misfolded proteins. The disrupted initiation of UPR prevents the elimination of unfolded proteins, leading to ER stress. In AD, the accumulation of misfolded proteins caused by sustained cellular stress leads to neurodegeneration and neuronal death. Current research has revealed that ER stress can trigger an inflammatory response through diverse transducers of UPR. Although the involvement of a neuroinflammatory component in AD has been documented for decades, whether it is a contributing factor or part of the neurodegenerative events is so far unknown. Besides, a feedback loop occurs between neuroinflammation and ER stress, which is strongly associated with neurodegenerative processes in AD. In this review, we focus on the current research on ER stress and UPR in cellular aging and neuroinflammatory processes, leading to memory impairment and synapse dysfunction in AD.
AB - One evident hallmark of Alzheimer's disease (AD) is the irregular accumulation of proteins due to changes in proteostasis involving endoplasmic reticulum (ER) stress. To alleviate ER stress and reinstate proteostasis, cells undergo an integrated signaling cascade called the unfolded protein response (UPR) that reduces the number of misfolded proteins and inhibits abnormal protein accumulation. Aging is associated with changes in the expression of ER chaperones and folding enzymes, leading to the impairment of proteostasis, and accumulation of misfolded proteins. The disrupted initiation of UPR prevents the elimination of unfolded proteins, leading to ER stress. In AD, the accumulation of misfolded proteins caused by sustained cellular stress leads to neurodegeneration and neuronal death. Current research has revealed that ER stress can trigger an inflammatory response through diverse transducers of UPR. Although the involvement of a neuroinflammatory component in AD has been documented for decades, whether it is a contributing factor or part of the neurodegenerative events is so far unknown. Besides, a feedback loop occurs between neuroinflammation and ER stress, which is strongly associated with neurodegenerative processes in AD. In this review, we focus on the current research on ER stress and UPR in cellular aging and neuroinflammatory processes, leading to memory impairment and synapse dysfunction in AD.
KW - Aging
KW - Alzheimer's disease
KW - Endoplasmic reticulum
KW - ER stress
KW - Neuroinflammation
KW - Unfolded protein response
UR - http://www.scopus.com/inward/record.url?scp=85111642020&partnerID=8YFLogxK
U2 - 10.1016/j.arr.2021.101417
DO - 10.1016/j.arr.2021.101417
M3 - Review article
C2 - 34339860
AN - SCOPUS:85111642020
SN - 1568-1637
VL - 70
JO - Ageing Research Reviews
JF - Ageing Research Reviews
M1 - 101417
ER -