title: HSPA5/Dna K may be a useful target for human disease therapies.
abstract: The chaperone protein HSPA5/Dna K is conserved throughout evolution from higher eukaryotes down to prokaryotes. The celecoxib derivative OSU-03012 (also called AR-12) interacts with Viagra or Cialis in eukaryotic cells to rapidly reduce HSPA5 levels as well as blunt the functions of many other chaperone proteins. Because multiple chaperones are modulated in eukaryotes, the expression of cell surface virus receptors is reduced and because HSPA5 in blocked viruses cannot efficiently replicate. Because DnaK levels are reduced in prokaryotes by OSU-03012, the levels of DnaK chaperone proteins such as Rec A decline, which is associated with bacterial cell death and a resensitization of so-called drug-resistant superbugs to standard of care antibiotics. In Alzheimer's disease, HSPA5 has been shown to play a supportive role for the progression of tau phosphorylation and neurodegeneration. Thus, in eukaryotes, HSPA5 represents a target for anticancer, antiviral, and anti-Alzheimer's therapeutics and in prokaryotes, DnaK and bacterial phosphodiesterases represent novel antibiotic targets that should be exploited in the future by pharmaceutical companies.
authors.affiliation: Department of Biochemistry and Molecular Biology, Virginia Commonwealth University , Richmond, Virginia.
authors.forename: Laurence
authors.initials: L
authors.lastname: Booth
authors.forename: Jane L
authors.initials: JL
authors.lastname: Roberts
authors.forename: Paul
authors.initials: P
authors.lastname: Dent
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D001424:Bacterial Infections / Q000378:metabolism / Q000517:prevention & control; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D055550:Protein Stability / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D014777:Virus Diseases / Q000378:metabolism / Q000517:prevention & control
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; C500894:OSU 03012; D011720:Pyrazoles; D013449:Sulfonamides