Target intelligence / Profile preview

Proteostasis network (PN) (PN)

Target
PN
Molecular classification
Enzyme, Chaperone, Receptor, Transporter, Other
01

Overview

The proteostasis network (PN) is an integrated system of biological pathways that control the biogenesis, folding, trafficking, and degradation of proteins within the cell (Balch et al., 2008). It ensures that the proteome remains functional and balanced, preventing the accumulation of misfolded or aggregated proteins which are toxic to cells (Hipp et al., 2019). Key components of the PN include molecular chaperones, the ubiquitin-proteasome system (UPS), and the autophagy-lysosome pathway (ALP) (Labbadia & Morimoto, 2015). Dysregulation of the PN is a hallmark of aging and is central to the pathogenesis of neurodegenerative diseases like Alzheimer's and Parkinson's, as well as various cancers and metabolic disorders (Klaips et al., 2018). Therapeutic strategies targeting the PN aim to either enhance the capacity of the network to handle misfolded proteins or selectively inhibit components, such as the 26S proteasome in cancer, to induce apoptosis in malignant cells (Powers et al., 2009).

Other names
Protein homeostasis networkProtein quality control systemPQC systemProteostasis system
02

Mechanism of action

Modulation of protein synthesis, folding, trafficking, and degradation pathways to maintain or restore proteome integrity (Balch et al., 2008).

03

Biological functions

Protein foldingProtein degradationProtein synthesisProtein traffickingCellular stress response
04

Disease associations

Neurodegenerative diseaseCancerCystic fibrosisMetabolic diseaseAging
05

Safety considerations

Systemic toxicity from broad inhibition of protein degradationPotential for neurotoxicityImpairment of essential cellular housekeeping functionsNarrow therapeutic window for proteasome inhibitors
06

Interacting drugs

Bortezomib

6 more in the full profile.

07

Biomarkers

Polyubiquitinated protein aggregatesHeat shock protein 70 (HSP70) levelsLC3-II levelsBinding immunoglobulin protein (BiP) levels

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