TABLE 1.
HSPs in CNS diseases
| Type | Function | Biologic activity | Pathologic | Preventive | AUC (au) | Reference |
|---|---|---|---|---|---|---|
| Hsp27 | Antiaggregation | Sustained angiogenesis (TLR3) VEGF release | GBM growth | 72, 147 | ||
| Antioxidative | Anti-inflammatory effect | Cortical spreading depression | 148, 149 | |||
| Antiapoptotic | BBB integrity (anti-actin polymerization) | I/R-induced neurovascular injury | 28 | |||
| Thermotolerance | Resistance to chemotherapeutics | GBM growth | 0.871 | 150, 151 | ||
| Prevent tau accumulation | Neurodegeneration (AD, PD, MS) | 152, 153 | ||||
| Neurite outgrowth, NSC/NPC differentiation | Neurodegeneration (AD, PD, MS) | 26, 153 | ||||
| Hsp40 | Protein folding | Hsp40/Hsp70 complex | Meningioma | 154 | ||
| Cochaperone of | Release of neurodegenerative proteins | AD, PD | 155, 156 | |||
| Hsp70 promoting | ||||||
| its ATPase activity | ||||||
| Hsp60 | Mitochondrial | Neuroinflammation (TLR4) | GBM, epilepsy, MS, ASD | 3, 157, 158 | ||
| Protein folding | Proliferation (mTOR pathway) | GBM | 158 | |||
| Hsp70 | Protein folding and | Neuro-inflammation (TLR4) | ASD | 0.987 | 159, 160 | |
| Membrane transport | Meningioma, GBM | 0.779 | 161 | |||
| Antiapoptotic | BBB disruption | ICH | 162 | |||
| Immunomodulatory | Transendothelial cell migration | ALS | 0.826 | 163 | ||
| Neuroinflammation (TLR2/TLR4) | Ischemic stroke | 68 | ||||
| Invasion, endocytosis | AD, glioma | 131 | ||||
| Anti-inflammatory and neuroprotective | AD, PD, HKD | 112, 115, 123 | ||||
| HSP90α | Folding of many | Cell proliferation | GBM | 164 | ||
| regulatory proteins | Migration (TLR4) | Cell invasion, metastasis | 66, 165 | |||
| Interaction with | Membrane deformation | Hyperthermia | 166 | |||
| signaling pathways | Fusion of MVBs with plasma membrane | Propagation (exosome) | 54 | |||
| Exosomal secretion | ||||||
| HSP110 | Protein | Reduce injury at the impact site | Traumatic brain injury | 167 | ||
| Disaggregation | Suppress cancer cell apoptosis | GBM growth | 169 | |||
| Stress tolerance | Prevent tau accumulation | Neurodegeneration (AD, PD, MS) | 168 | |||
| Increase levels of BDNF | Depression | 170 |
List of HSPs examined and their main chaperone functions, their biologic activity, including those interacting with TLRs, their involvement in CNS diseases (pathologic or preventive), and the AUC determined from biopsies fluid (plasma, cerebrospinal fluid, or both) that reflects the reliability of the HSP assay as biomarkers for early diagnosis in patients (3, 28, 54, 66, 68, 131, 147–170). ALS, amyotrophic lateral sclerosis; ASD, autism spectrum disorders; au., arbitrary units with values from 0 to 1; BDNF, brain-derived neurotrophic factor; HKD, Huntington’s and Kennedy’s diseases; ICH, intracerebral hemorrhage; IR, ischemia-reperfusion; MS, multiple sclerosis; PD, Parkinson’s disease.