Endoplasmic reticulum stress and unfolded protein response in neurodegenerative diseases
Date
2020Item Type
ArticleAbstract
The endoplasmic reticulum (ER) is an important organelle involved in protein quality
control and cellular homeostasis. The accumulation of unfolded proteins leads to an ER stress,
followed by an adaptive response via the activation of the unfolded protein response (UPR), PKR-like
ER kinase (PERK), inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) and
activating transcription factor 6 (ATF6) pathways. However, prolonged cell stress activates apoptosis
signaling leading to cell death. Neuronal cells are particularly sensitive to protein misfolding,
consequently ER and UPR dysfunctions were found to be involved in many neurodegenerative
diseases including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and prions
diseases, among others characterized by the accumulation and aggregation of misfolded proteins.
Pharmacological UPR modulation in affected tissues may contribute to the treatment and prevention
of neurodegeneration. The association between ER stress, UPR and neuropathology is well established.
In this review, we provide up-to-date evidence of UPR activation in neurodegenerative disorders
followed by therapeutic strategies targeting the UPR and ameliorating the toxic effects of protein
unfolding and aggregation.
Author
Ghemrawi, Rose
Khair, Mostafa