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The small heat shock protein (sHsp) family is a group of proteins in which some are induced in response to external stimuli, such as environmental and pathological stresses, while others are constitutively expressed. They show chaperone-like activity, protect cells from apoptosis, and maintain cytoskeletal architecture. Short sequences or fragments ranging from approximately 19-20 residues in sHsps were shown to display chaperone activity in vitro. These sequences are termed sHsp-derived mini-peptides/mini-chaperones. These peptides offer an advantage in providing protective and therapeutic effects over full-length proteins owing to their small molecular weight and easy uptake into the cells. Research on sHsp mini-chaperone therapy has recently received attention and advanced tremendously. sHsp mini-chaperones have shown a wide range of therapeutic effects, such as anti-aggregation of proteins, anti-apoptotic, anti-inflammatory, anti-oxidant, senolytic, and anti-platelet activity. The administration of mini-chaperones into the several disease animal models, including experimental autoimmune encephalomyelitis, cataract, age-related macular degeneration, glaucoma, and thrombosis through various routes reduced symptoms or prevented the progression of the disease. However, it was found that the therapeutic potential of sHsp mini-chaperones is limited by their short turnover and enzymatic degradation in circulation. Nonetheless, carrier molecules approach such as nanoparticles, cell penetration peptides, and extracellular vesicles increased their efficacy by enhancing the uptake, retention time, protection from enzymatic degradation, and site-specific delivery without altering their biological activity. In this context, this review highlights the recent advances in the therapeutic potential of sHsp-derived mini-chaperones, their effect in experimental animal models, and approaches for increasing their efficacy. • Short sequences/fragments ranging approximately 19–20 residues in small heat shock protein (sHsp) acts as mini-chaperones. • sHsps (Hsp27, αAC and αBC) derived mini-chaperones show protective and therapeutic effects in vitro and in vivo. • Carrier molecules such as nanoparticles, and protein polymers enhance the uptake and stability of mini-chaperones. • Delivery of the sHsps/their peptides with extracellular vesicles will offer a great opportunity as effective drug carriers. [ABSTRACT FROM AUTHOR]

The hierarchical information flow through DNA-RNA-protein-metabolite collectively referred to as ‘molecular fingerprint’ defines both health and disease. Environment and food (quality and quantity) are the key factors known to affect the health of an individual. The fundamental concepts are that the transition from a healthy condition to a disease phenotype must occur by concurrent alterations in the genome expression or by differences in protein synthesis, function and metabolites. In other words, the dietary components directly or indirectly modulate the molecular fingerprint and understanding of which is dealt with nutrigenomics. Although the fundamental principles of nutrigenomics remain similar to that of traditional research, a collection of comprehensive targeted/untargeted data sets in the context of nutrition offers the unique advantage of understanding complex metabolic networks to provide a mechanistic understanding of data from epidemiological and intervention studies. In this review the challenges and opportunities of nutrigenomic tools in addressing the nutritional problems of public health importance are discussed. The application of nutrigenomic tools provided numerous leads on biomarkers of nutrient intake, undernutrition, metabolic syndrome and its complications. Importantly, nutrigenomic studies also led to the discovery of the association of multiple genetic polymorphisms in relation to the variability of micronutrient absorption and metabolism, providing a potential opportunity for further research toward setting personalized dietary recommendations for individuals and population subgroups. [ABSTRACT FROM AUTHOR]

Inhibition of the 26S proteasome is an attractive approach for anticancer therapy. Proteasome inhibitors are known to selectively target cancer cells and make them more sensitive to chemotherapeutic agents. Murraya koenigii is a medicinally important herb of Asian origin and a rich source of bioactive compounds such as flavonoids and alkaloids. In the present study, we investigated the proteasome inhibitory and apoptotic effect of M. koenigii leaf extract in vivo in a xenograft tumor mouse model, and also assessed the toxicity if any in normal mice. M. koenigii extract did not lead to any toxicity in mice. Analysis of extract revealed the presence of flavonoid compounds which act as proteasome inhibitors. Quercetin treatment led to the decrease in the cell viability and arrest of cells in G2/M phase. Quercetin, Apigenin, Kaempferol and Rutin; flavonoids present in the leaf extract, dose-dependently inhibited the endogenous 26S proteasome activity in MDA-MB-231 cells. Reduction in tumor growth was associated with a decrease in proteasomal enzyme activities in the treated groups. Increased caspase-3 activity and TUNEL-positive cells indicated enhanced apoptosis with Murraya leaf extract treatment. Decreased expression of angiogenic and anti-apoptotic gene markers is indicative of inhibition of angiogenesis and promotion of apoptosis in the leaf extract treated tumors.

Previously we identified a novel mutation (F71L) in the αA-crystallin gene associated with early onset of age-related cataract. However, it is not known how the missense substitution translates into reduced chaperone-like activity (CLA), and how the structural and functional changes lead to early onset of the disease. Herein, we show that under native conditions the F71L-mutant is not significantly different from wild-type with regard to secondary and tertiary structural organization, hydrophobicity and the apparent molecular mass of oligomer but has substantial differences in structural and functional properties following a heat treatment. Wild-type αA-crystallin demonstrated increased CLA, whereas the F71L-mutant substantially lost its CLA upon heat treatment. Further, unlike the wild-type αA-subunit, F71L-subunit did not protect the αB-subunit in hetero-oligomeric complex from heat-induced aggregation. Moreover, hetero-oligomer containing F71L and αB in 3:1 ratio had significantly lower CLA upon thermal treatment compared to its unheated control. These results indicate that α-crystallin complexes containing F71L-αA subunits are less stable and have reduced CLA. Therefore, F71L may lead to earlier onset of cataract due to interaction with several environmental factors (e.g., temperature in this case) along with the aging process., (Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)