Pharmacological targeting of endoplasmic reticulum stress in disease.
Stefan John MarciniakJoseph E ChambersDavid RonPublished in: Nature reviews. Drug discovery (2021)
The accumulation of misfolded proteins in the endoplasmic reticulum (ER) leads to ER stress, resulting in activation of the unfolded protein response (UPR) that aims to restore protein homeostasis. However, the UPR also plays an important pathological role in many diseases, including metabolic disorders, cancer and neurological disorders. Over the last decade, significant effort has been invested in targeting signalling proteins involved in the UPR and an array of drug-like molecules is now available. However, these molecules have limitations, the understanding of which is crucial for their development into therapies. Here, we critically review the existing ER stress and UPR-directed drug-like molecules, highlighting both their value and their limitations.
Keyphrases
- endoplasmic reticulum
- endoplasmic reticulum stress
- induced apoptosis
- cancer therapy
- protein protein
- papillary thyroid
- amino acid
- binding protein
- high throughput
- drug induced
- small molecule
- adverse drug
- young adults
- oxidative stress
- breast cancer cells
- estrogen receptor
- lymph node metastasis
- drug delivery
- subarachnoid hemorrhage
- single cell