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| title | chunk | source | category | tags | date_saved | instance |
|---|---|---|---|---|---|---|
| Proteostasis | 3/3 | https://en.wikipedia.org/wiki/Proteostasis | reference | science, encyclopedia | 2026-05-05T07:16:30.910694+00:00 | kb-cron |
=== Pharmacologic intervention in proteostasis === There are two main approaches that have been used for therapeutic development targeting the proteostatic network: pharmacologic chaperones and proteostasis regulators. The principle behind designing pharmacologic chaperones for intervention in diseases of proteostasis is to design small molecules that stabilize proteins exhibiting borderline stability. Previously, this approach has been used to target and stabilize G-protein coupled receptors, neurotransmitter receptors, glycosidases, lysosomal storage proteins, and the mutant CFTR protein that causes cystic fibrosis and transthyretin, which can misfiled and aggregate leading to amyloidoses. Vertex Pharmaceuticals and Pfizer sell regulatory agency approved pharmacologic chaperones for ameliorating cystic fibrosis and the transthyretin amyloidoses, respectively. Amicus sells a regulatory agency approved pharmacologic chaperone for Fabry disease–a lysosomal storage disease. The principle behind proteostasis regulators is different. These molecules alter the biology of protein folding and/or degradation by altering the stoichiometry of the proteostasis network components in a given sub cellular compartment. For example, some proteostasis regulators initiate stress responsive signaling, such as the unfolded protein response, which transcriptionally reprograms the endoplasmic reticulum proteostasis network. It has been suggested that this approach could even be applied prophylactically, such as upregulating certain protective pathways before experiencing an anticipated severe cellular stress. One theoretical mechanism for this approach includes upregulating the heat shock response to rescue proteins from degradation during cellular stress.
== See also == Molecular chaperone therapy
== References ==