Abstract
Alzheimer’s, Huntington’s, and Parkinson’s are devastating neurodegenerative diseases that are prevalent in the aging population. Patient care costs continue to rise each year, because there is currently no cure or disease modifying treatments for these diseases. Numerous efforts have been made to understand the molecular interactions governing the disease development. These efforts have revealed that the phosphorylation of proteins by kinases may play a critical role in the aggregation of disease-associated proteins, which is thought to contribute to neurodegeneration. Interestingly, a molecular chaperone complex consisting of the 90 kDa heat shock protein (Hsp90) and Cell Division Cycle 37 (Cdc37) has been shown to regulate the maturation of many of these kinases as well as regulate some disease-associated proteins directly. Thus, the Hsp90/Cdc37 complex may represent a potential drug target for regulating proteins linked to neurodegenerative diseases, through both direct and indirect interactions. Herein, we discuss the broad understanding of many Hsp90/Cdc37 pathways and how this protein complex may be a useful target to regulate the progression of neurodegenerative disease.
Highlights
Molecular chaperones are important regulators of cellular homeostasis (Csermely et al, 1998; Buchner, 2013; Balchin et al, 2016; Lackie et al, 2017; Rosenzweig et al, 2019)
Recent reports suggest that the heat shock protein 90 (Hsp90)/Cell Division Cycle 37 (Cdc37) interaction is important in preventing activated kinase aggregation (Tripathi et al, 2014; Verba and Agard, 2017)
Lewy bodies primarily consist of misfolded α-synuclein. It has been suggested by our previous work that Cdc37 does not globally alter α-synuclein stability (Jinwal et al, 2011), but instead may contribute to the regulation of α-synuclein phosphorylation, which is highly linked to its aggregation
Summary
Molecular chaperones are important regulators of cellular homeostasis (Csermely et al, 1998; Buchner, 2013; Balchin et al, 2016; Lackie et al, 2017; Rosenzweig et al, 2019). Many kinases that are regulated by Cdc37 have been implicated in neurodegenerative disease-related pathways (Branca et al, 2017; Kirouac et al, 2017; Lackie et al, 2017; Lazarevic et al, 2017; Li and Götz, 2017; Yang et al, 2018; Zhang et al, 2018).
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