Role of Heat Shock Proteins in Diseases and Their Therapeutic Potential

Abstract

Heat shock proteins are ubiquitously expressed intracellular proteins and act as molecular chaperones in processes like protein folding and protein trafficking between different intracellular compartments. They are induced during stress conditions like oxidative stress, nutritional deficiencies and radiation. They are released into extracellular compartment during necrosis. However, recent research findings highlights that, they are not solely present in cytoplasm, but also released into extracellular compartment during normal conditions and even in the absence of necrosis. When present in extracellular compartment, they have been shown to perform various functions like antigen presentation, intercellular signaling and induction of pro-inflammatory cytokines. Heat shock proteins represents as dominant microbial antigens during infection. The phylogenetic similarity between prokaryotic and eukaryotic heat shock proteins has led to proposition that, microbial heat shock proteins can induce self reactivity to host heat shock proteins and result in autoimmune diseases. The self-reactivity of heat shock proteins protects host against disease by controlling induction and release of pro-inflammatory cytokines. However, antibodies to self heat shock proteins haven been implicated in pathogenesis of autoimmune diseases like arthritis and atherosclerosis. Some heat shock proteins are potent inducers of innate and adaptive immunity. They activate dendritic cells and natural killer cells through toll-like receptors, CD14 and CD91. They play an important role in MHC-antigen processing and presentation. These immune effector functions of heat shock proteins are being exploited them as therapeutic agents as well as therapeutic targets for various infectious diseases and cancers.

Effect of interleukin‐1β and lipoxin A4 in human endometriotic stromal cells: Proteomic analysis

“…40 HSP70 overexpression inhibits cell apoptosis and necrosis by interacting at several points in the apoptotic signaling pathway. [41][42][43] Serum HSP 70 is higher in patients with endometriosis compared with controls. 44,45 Similarly, ARHGDIA protein expression was significantly upregulated in the endometrial fluid aspirate of endometriosis stages III-IV compared with controls.…”

Advances in integrative nanomedicine for improving infectious disease treatment in public health

“…NPs from various natural products, with their enhanced bioavailability, act as hormetins to promote stronger neuroimmune function in the host organism [176, 235–237]. For example, homeopathic NPs can elicit cross-adapted and cross-sensitized hormetic heat shock protein response patterns [160, 161, 220] that would, among other effects, induce innate and adaptive immunity to combat infections and other diseases [238]. …”

Targeting Heat Shock Proteins 60 and 70 of Toxoplasma gondii as a Potential Drug Target: In Silico Approach

“…Hsps are phylogenetically conserved proteins that can be found in all species [12]. These proteins consist of six major families that are grouped according to their molecular weight: Hsp100, Hsp90, Hsp70, Hsp60, Hsp40, and small heat shock proteins (smHsps) [13].…”

“…These proteins consist of six major families that are grouped according to their molecular weight: Hsp100, Hsp90, Hsp70, Hsp60, Hsp40, and small heat shock proteins (smHsps) [13]. Hsps known as molecular chaperone, assist in correct folding of nascent proteins, facilitate protein translocation and degradation, and also involve in assembly and disassembly of protein complex [12]. They play critical roles during stress by repairing or denaturing the damaged proteins in order to restore protein homeostasis and promote cell survival [13].…”