Current Pharmaceutical Design - Volume 19, Issue 3, 2013

According to the “membrane sensor” hypothesis, the membrane’s physical properties and microdomain organization play an initiating role in the heat shock response. Clinical conditions such as cancer, diabetes and neurodegenerative diseases are all coupled with specific changes in the physical state and lipid composition of cellular membranes and characterized by altered heat shock protein levels in cells suggesting tha Read More

Hsp90 is a major molecular chaperone that is expressed abundantly and plays a pivotal role in assisting correct folding and functionality of its client proteins in cells. The Hsp90 client proteins include a wide variety of signal transducing molecules such as protein kinases and steroid hormone receptors. Cancer is a complex disease, but most types of human cancer share common hallmarks, including self-sufficiency in growth s Read More

Heat shock protein (Hsp) 90 is an ATP-dependent molecular chaperone which stabilizes various oncogenic kinases, including HER2, EGFR, BCR-ABL, B-Raf and EML4-ALK, which are essential for tumor growth. Several monoclonal antibodies and small molecule kinase inhibitors which target these kinases have been identified as potential new molecular target therapeutics. Previous reports have shown that many oncogenic proteins Read More

Combating stress is one of the prime requirements for any organism. For parasitic microbes, stress levels are highest during the growth inside the host. Their survival depends on their ability to acclimatize and adapt to new environmental conditions. Robust cellular machinery for stress response is, therefore, both critical and essential especially for pathogenic microorganisms. Microbes have cleverly exploited stress prot Read More

Human malaria is an economically important disease caused by single-celled parasites of the Plasmodium genus whose biology displays great evolutionary adaptation to both its mammalian host and transmitting vectors. While the parasite has multiple life cycle stages, it is in the blood stage where clinical symptoms of the disease are manifested. Following erythrocyte entry, the parasite resides in the parasitophorous v Read More

Heat shock protein 70 (Hsp70) plays critical roles in proteostasis and is an emerging target for multiple diseases. However, competitive inhibition of the enzymatic activity of Hsp70 has proven challenging and, in some cases, may not be the most productive way to redirect Hsp70 function. Another approach is to inhibit Hsp70’s interactions with important co-chaperones, such as J proteins, nucleotide exchange factors (NEFs) Read More

Mortalin is a member of Hsp70 family of stress chaperones. It was first identified as a protein involved in the senescence of mouse cells. Genetic studies revealed that there are two mouse mortalin alleles coding for two proteins (mot-1 and mot-2) that differ in only two amino acids in the carboxy-terminus, but have contrasting activities. Whereas mot-1 accelerated senescence, mot-2 extended the lifespan of mouse cells i Read More

Tumor specific cell surface localization and release of the stress inducible heat shock protein 70 (Hsp70) stimulate the immune system against cancer cells. A key immune stimulatory function of tumor-derived Hsp70 has been exemplified with the murine melanoma cell model, B16 overexpressing exogenous Hsp70. Despite the therapeutic potential mechanism of Hsp70 transport to the surface and release remained Read More

Heat shock proteins (HSPs) are ubiquitous and evolutionary conserved proteins induced by cell stress. HSP60, in particular, is a typical mitochondrial molecular chaperone that is known to assist nascent polypeptides to reach a native conformation. HSP60 is also known to interact with HSP10. In the last decade, HSP60 has been detected in the cytosol, the cell surface, the extracellular space, and biological fluids. H Read More

In this minireview we focus on Hsp60 as a target for anticancer therapy. We discuss the new concepts of chaperonopathies and chaperonotherapy and present information on Hsp60 localization in the cell membrane of human tumor cells. We describe novel mechanisms for Hsp60 reaching the extracellular environment that involve membrane-associated stages, as well as data on anti-Hsp60 antibodies found in human sera, bot Read More

Nitric oxide (•NO) is a physiological mediator of vasorelaxation constitutively synthesized by endothelial nitric oxide synthase. Because •NO has a short half-life, it is stored by proteins through S-nitrosation reactions. S-nitrosation was recently defined as a post-translational modification of proteins for cellular signalling, as important as glycosylation and phosphorylation. Disulfide forming/ isomerizing enzymes like thioredoxi Read More

Heat shock proteins (HSPs) are involved in a number of cellular processes, including cell cycle, growth, and survival, apoptosis, stress responses, angiogenesis, and oncogenesis. Among the characterized HSPs, the molecular chaperone HSP90 has emerged as an exciting molecular target for cancer therapy since its discovery as the target protein of the antibiotic geldanamycin. The stress-inducible HSP70, which is upregulated Read More

Superparamagnetic iron oxide nanoparticles (SPIONs) comprise a fundamental technology class within the emerging field of nanomedicine, and have been extensively researched for cancer imaging and therapy. This review article will discuss the chemistry and design considerations associated with the synthesis of SPIONs and their incorporation into pharmaceutical formulations. Specific synthesis methods discussed i Read More

Pharmacological treatment of disorders affecting the central nervous system (CNS) is a complex task. Different parameters may negatively influence effective targeting of the CNS and drug compliance, for example, poor brain-blood barrier (BBB) permeability, patient forgetfulness or neglect, and lack of collaboration between caregivers and patients. Pharmaceutical science is constantly looking for new administration Read More