Table 1.
List of extracellular chaperones and their substrate specificity and regulation
| Extracellular chaperone | Gene | In vivo substrate specificity | Regulation during stress |
|---|---|---|---|
| 7B2 | SCG5 | Aβ in AD plaques; α-synuclein in Lewy bodies | Promoter contains heat shock element–like sequences but function not explored (Braks et al., 1996) |
| α2-Macroglobulin | A2M | β2-Microglobulin | Induced by the acute phase response (Ehlting et al., 2021) |
| αB crystallin | CRYAB | Broad intracellular substrate specific | Induced by the heat shock response; normally an intracellular protein (Ryno et al., 2014) |
| β-Casein | CSN2 | Milk proteins, amyloid, and nonamyloid aggregates | Induced in mammary epithelial cells by lactogenic hormones; heat stressing cultured mammary cells increases production via the UPR (Mizusawa et al., 2019) |
| Brichos-domain containing proteins | BRI1, BRI2 | Intramolecular in pulmonary surfactant C, AD plaques | Undefined |
| Clusterin | CLU | Broad substrate specificity | Induced by the heat shock response and oxidative stress; relocalized to the cytosol during ER stress (Nizard et al., 2007; Li et al., 2013; Niforou et al., 2014) |
| ERdj3/DNAJB11 | DNAJB11 | Broad substrate specificity | Induced by the UPR; increased secretion during ER stress (Genereux et al., 2015) |
| Haptoglobin | HP | Hemoglobin | Induced by the acute phase response (Ehlting et al., 2021) |
| HSPB1 | HSPB1 | Mutations associated with hereditary neuropathies, associated with Tau in tauopathies | Induced by the heat shock response; normally an intracellular protein (Ryno et al., 2014) |
| Neuroserpin | SERPINI1 | Amyloid plaques in AD | Undefined |
| Progranulin | GRN | Cathepsin D, β-glucocerebrosidase | Induced during hypoxia and exercise (Wang et al., 2021) |
| ProSAAS | PCSK1N | Neurodegenerative diseases, AD, Parkinson’s, Pick’s | Induced during ER and heat stress; secretion is reduced under these conditions (Shakya et al., 2020) |
| S100A proteins | S100A1-A16 | Aβ in plaques; breadth not clear | Induced in response to diverse inflammatory and oxidative insults (Gonzalez et al., 2020) |
| Transthyretin | TTR | Amyloid fibrillogenesis | Induced by the heat shock response in brain, but not liver (Wang et al., 2014) |