When cells accumulate ER stresses, ER chaperone proteins can be induced to alleviate protein aggregation and activate the proteosome machinery to degrade misfolded proteins.
For survival, the cells induce endoplasmic reticulum chaperone proteins to alleviate protein aggregation, transiently attenuate translation and activate the proteosome machinery to degrade misfolded proteins.
When cells accumulate ER stresses, ER chaperones can be induced to alleviate protein aggregation and activate the proteosome machinery to degrade misfolded proteins.
The protein kinase RNA (PKR -like ER kinase (PKR -likea critical initiator of UPR signalling, which attERpts to restore normal ER function by inhibiting general protein synthesis while promoting transcription of ER chaperones and folding enzymes to enhance ER processing and alleviate protein aggregation (Yang and Paschen, 2009).
Thus, the upregulation of the chaperone BiP, as part of the UPR response, would increase the protein folding activity and prevent protein aggregation, alleviating the ER stress induced by impaired glycosylation [ 142].
For example, HSP70 has been shown to reduce protein aggregation and alleviate disease phenotypes in various neurodegenerative disorders, including Alzheimer's disease (Bobkova et al., 2014), amyotrophic lateral sclerosis (Gifondorwa et al., 2012), and tauopathies (Jinwal et al., 2013).
We demonstrated that flurbiprofen, a nonsteroidal anti-inflammatory drug (NSAID), exhibited chaperone activity, which reduced protein aggregation and alleviated ER stress-induced leptin resistance, characterized by insensitivity to the actions of the anti-obesity hormone leptin.
Stefani, M. & Dobson, C. M. Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution.
To our surprise, a reduction in global translation rates of only two codons CAA and AAA led to widespread protein aggregation and imbalanced protein homeostasis, defects alleviated solely by restoring decoding speed.
Protein kinase a regulates molecular chaperone transcription and protein aggregation.
Molecular thermodynamic model for helix-helix docking and protein aggregation.
