HSP70 and HSP90 in neurodegenerative diseases

Abstract

Molecular chaperones have a role to stabilize proteins or assist them in reaching their native fold. Heat shock proteins (HSPs) are a family of molecular chaperons that protect proteins from cellular stress during the assembly of protein complexes and also prevent the proteins from aggregation and disassembly. The immediate increase of HSPs is crucial for cellular adaptation to environmental changes and protection of other proteins from denaturation, thereby maintaining the cellular homeostasis and increasing the longevity of an organism. HSP70 and HSP90 are the most studied HSPs in this very large HSP family. Notably, HSP90 also stabilizes the disease-related proteins in neurodegenerative disorders. Therefore, small molecules that inhibit the HSP90 but also increase the HSP70 has been tested as potential drugs for neurodegenerative disorders.

Transcriptional Profiles of Cell Fate Transitions Reveal Early Drivers of Neuronal Apoptosis and Survival

“…On the other hand, delayed early response genes were enriched in functions related to many cellular processes, including cytoskeleton organization, response to DNA damage, cell adhesion and metabolic processes, suggesting their regulation may function as effectors of the transcriptional program governing neuronal fate decision (Figure 4). Interestingly, among these latter is Ahsa2, a gene encoding a co-chaperone that stimulates HSP90, an inducible molecular chaperone protecting neurons in neurodegenerative diseases, such as Alzheimer's disease [46][47][48]. We found Ahsa2 dynamically activated by GFs at 1 and 3 h following apoptotic induction.…”

Inhibitors of the Plasmodium falciparum Hsp90 towards Selective Antimalarial Drug Design: The Past, Present and Future

“…When geldanamycin was first identified as a potent Hsp90 inhibitor, its derivatization soon ensued, and many more Hsp90 inhibitors were developed. These efforts were mainly driven by the essential role that Hsp90 plays in eukaryotes and its implication in various diseases, such as numerous cancers and parasitic diseases [ 185 , 186 ]. The biggest limitation with Hsp90 inhibitors apart from drug-like properties has been that they target closely related paralogs due to the high degree of sequence and structural similarities between paralogs and orthologs.…”

Roles of Cannabidiol in Reversing Proteinopathies

“…Recently, Scott et al showed that CBD treatment modulated HSPs expression, notably upregulated HSP70 and HSP90 in glioma cell lines [263]. Substantial evidence highlighted the critical roles of HSP70 and HSP90 in the quality control and clearance of the misfolded and aggregated proteins by the ubiquitin-proteasome system and chaperone machinery [264]. Additional observation by Rodríguez-Muñoz et al stated that CBD act as an antagonist of σ1R, which has been identified as a master regulator of proteostasis system [265].…”