The Role of Heat Shock Proteins in Reproductive Functions
Heat shock response (HSR) pathway is a highly conserved cellular process. Heat shock factor 1 (HSF1) is a master transcriptional regulator responsible for expression of several important heat shock proteins (HSPs), which can effectively protect critical c
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Abstract Introduction Heat shock response (HSR) pathway is a highly conserved cellular process. Heat shock factor 1 (HSF1) is a master transcriptional regulator responsible for expression of several important heat shock proteins (HSPs), which can effectively protect critical client proteins from misfolding and degradation, thus maintaining intracellular integrity under stressed conditions. Recent studies have demonstrated the direct connections between HSR players and tumor cell survival, validating HSR players as novel molecular targets in anticancer treatment. Small molecule screening has produced some promising HSR inhibitors for anticancer treatment. In this article, we will be summarizing the main findings from HSR inhibitors on recent clinical and preclinical studies. Methods The authors reviewed all the relevant papers of HSR inhibitors with an emphasis on human and animal studies. A. A.-A. Swelum (*) Department of Animal production, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia Department of Theriogenology, Faculty of Veterinary Medicine, Zagazig University, Sharkia, Egypt e-mail: [email protected]; [email protected]; [email protected] N. M. Hashem Animal and Fish Production Department, Faculty of Agriculture, Alexandria University, Alexandria, Egypt A. I. Abo-Ahmed Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Benha University, Toukh, Egypt M. E. Abd El-Hack Department of Poultry, Faculty of Agriculture, Zagazig University, Zagazig, Egypt M. Abdo Department of Anatomy and Embryology, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, Egypt © Springer Nature Switzerland AG 2020 A. A. A. Asea, P. Kaur (eds.), Heat Shock Proteins, https://doi.org/10.1007/7515_2020_32
A. A.-A. Swelum et al.
Results More than 18 unique chemical identities have been discovered with confirmed inhibition of HSR pathway. Among them, two natural products and their derivatives are currently in various phases of clinical studies. Detailed works are required to define the exact mechanisms of actions (MOA) for these compounds. Conclusions Many hurdles in clinical application still need to be effectively addressed, such as undesirable drug toxicity and off target effects; narrow therapeutic window; poor pharmacokinetic/pharmacodynamic (PK/PD) profiles, etc. Recent reports on synergistic drug combination, advanced prodrug design, smart nanoparticle packaging, and ribonucleic acid (RNA) aptamer selection offer promising solutions to overcome these challenges. Future advancements in this fast-growing area can potentially lead to the next-generation cancer therapeutics. Keywords Fertility · Heat shock proteins · Oocyte · Reproduction · Sperm
Abbreviations ART CD CDC DCs DNA HbA1c HELLP HSF HSFY HSPs HSR ICSI IVF LOX MOA NK NO NOS PK/PD RNA ROS Th TNF VDAC2
assisted reproductive technology Cluster of differentiation Cell division control Dendritic cells Deoxyribonucleic acid glycated hemoglobin H (hemolysis), EL (elevated liver enzymes), LP (low platel
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