Hsp70 Inducer Therapies For Neurodegeneration is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
HSP70 Inducer Therapies for Neurodegeneration [1]
| Property | Value | [2]
|----------|-------| [3]
| Category | Disease-Modifying Therapy | [4]
| Target | Hsp70 (HSPA1A, HSPA8), Hsp40 co-chaperones | [5]
| Diseases | Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, ALS, FTD | [6]
| Mechanism | Induce Hsp70 expression to enhance protein quality control and clearance of misfolded proteins | [7]
| Development Stage | Preclinical to Phase I |
Heat shock protein 70 (Hsp70) is a major molecular chaperone essential for protein quality control. Hsp70 induction represents a therapeutic strategy to enhance the cell's ability to refold misfolded proteins and clear aggregates in neurodegenerative diseases.
| Protein | Gene | Location | Function |
|---|---|---|---|
| Hsp70 (HSPA1A) | HSPA1A | Cytosol/Nucleus | Stress-inducible chaperone |
| Hsc70 (HSPA8) | HSPA8 | Cytosol/ER/Lysosomes | Constitutive chaperone |
| Grp78/BiP | HSPA5 | ER lumen | Unfolded protein response |
| mtHsp70 (Grp75) | HSPA9 | Mitochondria | Mitochondrial protein import |
| Compound | Mechanism | Status |
|---|---|---|
| Arimoclomol | HSF1 co-activator | Phase III (ALS) |
| Celastrol | HSF1 activator | Preclinical |
| 17-DMAG | Hsp90 inhibitor | Preclinical |
| Geldanamycin derivatives | Hsp90 inhibitor | Research |
| Compound | Target | Status |
|---|---|---|
| 2-phenylethynesulfonamide (PES) | Hsp70 | Research |
| YTL-HE-71 | Hsp70 | Preclinical |
| HSF1A | HSF1 | Research |
| Compound | Source | Mechanism |
|---|---|---|
| Curcumin | Turmeric | HSF1 activation |
| Resveratrol | Grapes | SIRT1/HSF1 |
| Quercetin | Various fruits | HSF1 activation |
Hsp70 inducers address:
Preclinical evidence:
Target:
Studies show:
Benefits:
Arimoclomol (BRL-5906):
The study of Hsp70 Inducer Therapies For Neurodegeneration has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Kieran D, et al. Treatment with arimoclomol, a coinducer of heat shock proteins, delays disease progression in ALS mice. Nature Medicine. 2004. ↩︎
Calamini B, et al. Small-molecule proteostasis regulators for treatment of human disease. Nature Chemical Biology. 2011. ↩︎
Balch WE, et al. Adapting proteostasis for disease intervention. Science. 2008. ↩︎
Chen Y, et al. Heat shock protein 70 in neurodegenerative diseases. Neuroscience Bulletin. 2011. ↩︎
Muchowski PJ, et al. The Hsp70 and Hsp40 molecular chaperones enable disassemblase activity. Proceedings of the National Academy of Sciences. 2000. ↩︎
Procaccia V, et al. HSF1 activation by small molecules. Journal of Molecular Neuroscience. 2020. ↩︎
Broadley SA, et al. Hsp70 and neurodegeneration. Brain Research Reviews. 2021. ↩︎