The use of sucrose-alternative sweeteners in ice cream production could satisfy requirements of modern consumers focused on natural and nutritionally …

The results suggest that trehalose may have antidepressant-like properties. It is hypothesized that these behavioral changes could be related to trehalose effects to enhance autophagy.

Alzheimer's disease is an irreversible and progressive brain disorder featured by the accumulation of Amyloid-β (Aβ) peptide, which forms insoluble assemblies that builds up into plaques resulting in cognitive decline and memory loss. The formation of fibrillar amyloid deposits is accompanied by con …

Our findings demonstrate that trehalose, functioning as an autophagy enhancer, suppresses the inflammatory response by promoting autophagic flux via TFEB activation in primary HCECs exposed to hyperosmotic stress, a process that is beneficial to dry eye.

(2017). Trehalose induces functionally active conformation in the intrinsically disordered N-terminal domain of glucocorticoid receptor. Journal of Biomolecular Structure and Dynamics: Vol. 35, No. 10, pp. 2248-2256.

Human cytomegalovirus (HCMV) is the top viral cause of birth defects worldwide, and current therapies have high toxicity. We previously reported that the mTOR-independent autophagy-inducing disaccharide trehalose inhibits HCMV replication in multiple cell types. Here, we examine the mechanism of inh …

Cutaneous melanomas frequently metastasize to the brain, with temozolomide (TMZ) plus radiotherapy (RT) offering little control of these lesions. We tested whether trehalose, a natural glucose disaccharide proved to induce autophagy, could enhance the effect of TMZ and ionizing radiation (IR). In tw …

Autophagy is required for neurulation, and autophagy activators with minimal toxicity, such as the natural compound trehalose, a nonreducing disacchar…

Insulin resistance is associated with cardiovascular diseases although the precise mechanisms remain elusive. Akt2, a critical member of the Akt famil…

The preservation of nucleic acids from clinical samples is critical to facilitate accurate molecular diagnosis. The use of a paper matrix, Flinders Technology Associates (FTA) Elute cards, to archive DNA and viral RNA is well-documented. However, the feasibility of FTA Elute cards for archiving seru …

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates a cluster of oxidative stress-inducible genes in cells. Here, we aimed to investigate whether trehalose (Tr...

Cadmium (Cd), as a kind of ubiquitous and highly toxic heavy metal pollutants, has been known to result in immunotoxicity in animals. As a multifuncti…

Purpose Phase separation of trehalose during freeze-drying could render it ineffective as a lyoprotectant. The bulking agent, mannitol, on the other hand, should crystallize readily upon freezing. It is therefore imperative to understand the mutual interaction of these sugars during freezing to ensure preservation of the API during freeze-drying. Methods We investigated the effect of mannitol to trehalose ratio (R) on the crystallization behavior of both solutes using Differential Scanning Calorimetry, X-Ray Crystallography and FTIR Spectrosopy during controlled freezing and annealing. Results When R = 1, crystallization of both mannitol (as hemihydrate) and trehalose (as α-anhydrate) were observed. When R ≥ 1, extent of mannitol crystallization was directly proportional to the value of R. When R  1, the freeze concentrate was heterogeneous and characterized by two glass transitions – the lower temperature transition (Tg”) attributed to systems containing “extra” unfrozen water. When heated above Tg”, crystallization of mannitol and the associated unfrozen water resulted in Tg’ (glass transition temperature of the freeze-concentrate). Conclusions R and not the total solute concentration, dictates the composition of the freeze concentrate as well as the physical stability of the excipients

The UVB-irradiated cornea is damaged by oxidative stress. Toxic oxygen products induced by UVB radiation in the cornea are insufficiently removed by antioxidants, whose numbers decrease with increasing UVB irradiation. In addition, the UVB-irradiated cornea suffers from hypoxic conditions because da …

This work reports several novel autophagy-lysosome modulators that enhance PGRN expression and identifies trehalose as a promising therapeutic for raising PGRN levels to treat multiple neurodegenerative diseases.

In this study, pH responsive genipin-cross-linked Pluronic F127-chitosan nanoparticles (GNPs) was synthesized to encapsulate trehalose for intracellular delivery to cryopreserve primary human adipose-derived stem cells (hADSCs). Trehalose is a disaccharide of glucose used by lower organisms to survi …

Developing effective theranostic nanoplex platforms for personalized disease treatment necessitates an understanding of and the ability to control live cell–nanoparticle interactions. However, aggregation of nanoparticles on the cell surface and their subsequent internalization is sparsely understood and adv

Trehalose is a natural disaccharide that is found in a diverse range of organisms but not in mammals. Autophagy is a process which mediates the sequestration, lysosomal delivery and degradation of proteins and organelles. Studies have shown that trehalose exerts beneficial effects through inducing autophagy in mammalian cells. However, whether trehalose or other saccharides can activate autophagy in keratinocytes is unknown. Here, we found that trehalose treatment increased the LC3-I to LC3-II conversion, acridine orange-stained vacuoles and GFP-LC3B (LC3B protein tagged with green fluorescent protein) puncta in the HaCaT human keratinocyte cell line, indicating autophagy induction. Trehalose-induced autophagy was also observed in primary keratinocytes and the A431 epidermal cancer cell line. mTOR signalling was not affected by trehalose treatment, suggesting that trehalose induced autophagy through an mTOR-independent pathway. mTOR-independent autophagy induction was also observed in HaCaT and HeLa cells treated with sucrose or raffinose but not in glucose, maltose or sorbitol treated HaCaT cells, indicating that autophagy induction was not a general property of saccharides. Finally, although trehalose treatment had an inhibitory effect on cell proliferation, it had a cytoprotective effect on cells exposed to UVB radiation. Our study provides new insight into the saccharide-mediated regulation of autophagy in keratinocytes.

A mouse study found that the natural sugar trehalose may be able to treat fatty liver disease, a condition partially caused by sugar consumption.

Trehalose, a natural disaccharide, inhibits short-term cell proliferation and, even more, colony-forming capacity in melanoma cells. Moreover, trehalose magnifies temozolomide (TMZ)- and irradiation ...

Atherosclerosis and nonalcoholic fatty liver disease (NAFLD) are frequent causes of death in the Western countries. Recently, it has been shown that autophagy dysfunction plays an important role in the pathogenesis of both atherosclerosis and NAFLD; thus, activators of autophagy might be useful for novel therapeutic interventions. Trehalose—a naturally occuring disaccharide present in plants, bacteria, fungi, insects, and certain types of shrimps—is a known inducer of autophagy. However, according to the literature, its anti-atherosclerotic and anti-steatotic potential seem to depend on the experimental setting. The aim of our study was to comprehensively describe the influence of a prolonged treatment with orally administered trehalose on the development of atherosclerotic lesions and hepatic steatosis in apolipoprotein E knockout (apoE−/−) mice in an experimental set up reflecting both moderate and severe proatherogenic conditions: male apoE−/− mice on a chow diet (CD) and female apoE−/− mice fed with a high-fat diet (HFD). We found that exogenous trehalose inhibited atherosclerosis and attenuated hepatic steatosis in apoE−/− mice. Such effects of trehalose were not associated with changes of plasma cholesterol, low-density lipoproteins (LDL), or high-density lipoproteins (HDL). Moreover, the anti-steatotic action of trehalose in the liver was associated with the induction of autophagy. The exact molecular mechanisms of both the anti-atherosclerotic action of trehalose and its inhibitory effect on liver steatosis require further clarification.

Autophagy is a catabolic process to maintain intracellular homeostasis via removal of cytoplasmic macromolecules and damaged cellular organelles through lysosome-mediated degradation. Trehalose is often regarded as an autophagy inducer, but we reported previously that it could prevent ischemic insul …

Trehalose is a non-reducing disaccharide formed by two glucose molecules. It is widely distributed in Nature and has been isolated from certain species of bacteria, fungi, invertebrates and plants, which are capable of surviving in a dehydrated state for months or years and subsequently being revived after a few hours of being in contact with water. This disaccharide has many biotechnological applications, as its physicochemical properties allow it to be used to preserve foods, enzymes, vaccines, cells etc., in a dehydrated state at room temperature. One of the most striking findings a decade ago was the discovery of the genes involved in trehalose biosynthesis, present in a great number of organisms that do not accumulate trehalose to significant levels. In plants, this disaccharide has diverse functions and plays an essential role in various stages of development, for example in the formation of the embryo and in flowering. Trehalose also appears to be involved in the regulation of carbon metabolism and photosynthesis. Recently it has been discovered that this sugar plays an important role in plant-microorganism interactions.

Autophagy is a highly conserved recycling pathway that promotes cell survival during periods of stress. We previously reported that induction of autophagy through the inhibition of the mechanistic target of rapamycin (MTOR) inhibits HIV replication in human macrophages and CD4+ T lymphocy …

Protein aggregation has been proved to be a pathological basis accounting for neuronal death caused by either transient global ischemia or oxygen glucose deprivation (OGD), and inhibition of protein aggregation is emerging as a potential strategy of preventing brain damage. Trehalose was found to inhibit protein aggregation caused by neurodegenerative diseases via induction of autophagy, whereas its effect is still elusive on ischemia-induced protein aggregation. In this study, we investigated this issue by using rat model of transient global ischemia and SH-SY5Y model of OGD. We found that pretreatment with trehalose inhibited transient global ischemia-induced neuronal death in the hippocampus CA1 neurons and OGD-induced death in SH-SY5Y cells, which was associated with inhibition of the formation of ubiquitin-labeled protein aggregates and preservation of proteasome activity. In vitro study showed that the protection of trehalose against OGD-induced cell death and protein aggregation in SH-SY5Y cells was reversed when proteasome activity was inhibited by MG-132. Further studies revealed that trehalose prevented OGD-induced reduction of proteasome activity via suppression of both oxidative stress and endoplasmic reticulum stress. Particularly, our results showed that trehalose inhibited OGD-induced autophagy. Therefore, we demonstrated that proteasome dysfunction contributed to protein aggregation caused by ischemic insults and trehalose prevented protein aggregation via preservation of proteasome activity, not via induction of autophagy.

The accumulation of lipids in hepatocytes that occurs in nonalcoholic fatty liver disease (NAFLD) can result in liver failure or liver cancer. Trehalose is a ubiquitous sugar that is present in the food consumed by animals. DeBosch et al . determined that trehalose blocked glucose uptake into cells by inhibiting glucose transporters in the plasma membrane, which induced a “starvation”-like response that activated autophagy even in the presence of adequate nutrients and glucose. Furthermore, providing trehalose to mice that are a model of NAFLD prevented lipid accumulation in the liver. As noted by Mardones et al . in the associated Focus, trehalose, which has been previously under investigation to treat neurodegenerative diseases characterized by toxic protein aggregates, may be a “silver bullet” for treating diseases resulting from inadequate cellular degradative metabolism. Trehalose is a naturally occurring disaccharide that has gained attention for its ability to induce cellular autophagy and mitigate diseases related to pathological protein aggregation. Despite decades of ubiquitous use as a nutraceutical, preservative, and humectant, its mechanism of action remains elusive. We showed that trehalose inhibited members of the SLC2A (also known as GLUT) family of glucose transporters. Trehalose-mediated inhibition of glucose transport induced AMPK (adenosine 5′-monophosphate–activated protein kinase)–dependent autophagy and regression of hepatic steatosis in vivo and a reduction in the accumulation of lipid droplets in primary murine hepatocyte cultures. Our data indicated that trehalose triggers beneficial cellular autophagy by inhibiting glucose transport.