Trehalose

During an investigation of subvisible particles found in lyophilized formulations of intravenous immunoglobulin, we used resonant mass measurement tec…

Countries worldwide have confirmed a staggering number of COVID-19 cases, and it is now clear that no country is immune to the SARS-CoV-2 infection. Resource-poor countries with weaker health systems are struggling with epidemics of their own and are now in a more uncertain situation with this rapidly spreading infection. Frontline healthcare workers are succumbing to the infection in their efforts to save lives. There is an urgency to develop treatments for COVID-19, yet there is limited clinical data on the efficacy of potential drug treatments. Countries worldwide implemented a stay-at-home order to “flatten the curve” and relieve the pressure on the health system, but it is uncertain how this will unfold after the economy reopens. Trehalose, a natural glucose disaccharide, is known to impair viral function through the autophagy system. Here, we propose trehalose as a potential preventative treatment for SARS-CoV-2 infection and transmission.

A widespread epidemic of Zika virus (a mosquito-borne flavivirus) infection was reported from 2015 in South and Central America. A major concern associated with the infection is the significantly increased incidence of microcephaly in fetuses born to the mothers infected with Zika virus (Mlakar et al., 2016). Researchers studying monkeys have shown that one infection with Zika virus protects the animal against future infections. Neutralizing antibodies are detected at 21 days post infection. Re-challenge at 10 weeks after the initial inoculation resulted in no detectable viral replication, indicating successfully protective immunity against the virus (Dudley et al., 2016). They also found that non-pregnant animals could clear the virus within 10 days post infection, however the virus persisted in the blood of pregnant monkeys for 35 to 70 days (Dudley et al., 2016). One possible explanation for the persistence of the virus in pregnancy is that the immune system of the mother was compromised, and she simply was not able to clear the virus as fast as the non-pregnant one. However the pregnant animal (woman) still has a certain level of immunity. Both type I interferons and type III interferons are apparently induced by Zika virus infections, and the interferons have an ability to restrict Zika virus replication in human trophoblast cells (Bayer et al., 2016; Quicke et al., 2016). The other explanation, more provocative hypothesis is that the persistence of the virus is indic...

(2021). A head-to-head comparison review of biological and toxicological studies of isomaltulose, d-tagatose, and trehalose on glycemic control. Critical Reviews in Food Science and Nutrition. Ahead of Print.

Our findings indicate that trehalose may be a useful saccharide for good health because of properties that do not stimulate rapid increases in blood glucose and excessive secretion of insulin and GIP promoting fat accumulation.

Novel liposomes composed of L-α-dimyristoylphosphatidylcholine (DMPC) and trehalose surfactant (DMTreCn) were produced by the method of sonication in buffer solution. The thickness of fixed aqueous layer of DMTreCn was larger than that of DMPC liposomes and increased in a dose-dependent manner. The remarkable inhibitory effects of DMTreCn on the growth of human hepatocellular carcinoma (HCC) (Hep-G2 and HuH-7) cells were obtained along with apoptosis, without affecting the growth of normal cells. DMTreCn induced apoptosis of Hep-G2 and HuH-7 cells through the activation of caspase-3, 8 and 9. Release of cytochrome c from mitochondria and activation of Bcl-2 family protein (BAX) were recorded, indicating that DMTreCn induced apoptosis of Hep-G2 and HuH-7 cells through mitochondrial pathway via BAX. It is noteworthy that the remarkable inhibitory effects of DMTreCn on the growth of human HCC cells were obtained along with apoptosis for the first time.

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

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 …

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.

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.

Trehalose is revered for its multiple unique impacts on solution properties, including the ability to modulate the salty and bitter tastes of sodium a…

Two field experiments were conducted during two successive seasons (2014/2015 and 2015/2016) at the Experimental Station of National Research Centre, Nubaria district, Beheira Governorate, Egypt, to study the effect of foliar treatment of quinoa plants with trehalose (Tre) (100µM and 500µM) on growth, photosynthetic pigments, seed yield quantity & quality, in fever of nutritional and antioxidant compounds in the yielded quinoa seeds which subjected to water deficiency (skipping two irrigation times at 50 & 60 days after sowing). Water deficiency caused marked decreases in quinoa plant growth parameters (shoot height, fresh and dry weights of shoot/plant) and photosynthetic pigments with marked increases in root growth parameters (root length, fresh and dry weight of root/plant). Drought stress decreased yield and yield attributes, carbohydrates, protein, nitrogen, phosphorous and potassium contents.  Meanwhile oil percentage, phenolic and flavonoids contents increased by drought stress. Antioxidant activity at 50 and 100µg/l showed significant increases in response to drought stress. On the other hand, Tre treatments proved to be effective in enhancing growth parameters and photosynthetic pigments of drought stressed plants. Trehalose treatments at different levels caused marked increases in yield and yield attributes, carbohydrate, protein, oil, nitrogen, phosphorous, potassium, total phenolic, flavonoids contents, and antioxidant activity of the yielded seeds either in non stressed or drought stressed plants relative to corresponding controls. Generally, 500 µM Tre was the most pronounced and effective treatment in alleviating the deleterious effect of drought stress on quinoa plants.

Abnormal denaturation and aggregation of human amylin or islet amyloid polypeptide (IAPP) into amyloid fibrils has been implicated in the pathogenesis of type 2 diabetic mellitus. Trehalose, a super-hydrophilic molecule, has been shown to prevent denaturation of biomolecules when they are under environmental stress

Trehalose is a disaccharide which plays an important role in preserving cells from completely dehydrated circumstances. In this study, we investigated effects of trehalose on proliferative activity of fibroblasts and epithelial cells both in vitro and in vivo. As in vitro assessment, normal human de …

Purpose. To investigate the inhibitory effects of trehalose on malignant melanoma cell growth. Methods. We cultured human malignant melanoma cells in a medium containing trehalose (control/2.5%/5.0%/7.5%/10.0%) and used the MTT assay to evaluate the growth activities. Subsequently, trehalose was topically instilled on subconjunctivally inoculated melanoma cells in F334/NJcl-rmu/rmu rats, followed by a histopathological evaluation of tumor growth. Using flow cytometry, we compared the distribution of the cell cycle, rate of apoptotic cells, and intracellular factors related to the cell cycle in cultured melanoma cells after trehalose treatment. Results. The MTT study showed that proliferation of melanoma cells was significantly inhibited by ≧ 5% of trehalose concentrations in the culture media. Subconjunctivally inoculated melanoma cell masses were significantly smaller in eyes administered trehalose as compared to controls. Flow cytometry analyses demonstrated that the trehalose groups had increased rates of G2/M phase cells and apoptotic cells in the cell culture. These cells also exhibited increased expressions of cell-cycle inhibitory factors. Conclusions. The current results show trehalose inhibits malignant melanoma cell growth by inducing G2/M cell cycle arrest and apoptosis, suggesting trehalose as a potential candidate for a topical agent to inhibit proliferation of malignant tumor cells of the ocular surface.

Objective: To assess the safety and efficacy of weekly IV administration of Cabaletta (trehalose 9\[percnt] solution) in OPMD after a 24 week open label phase 2 trial. Background: Trehalose showed efficacy in reducing PABPN1 muscle aggregation and improving muscle function in a transgenic OPMD mouse model. Methods:25 genetically-confirmed OPMD patients received weekly infusion of 300 cc Cabaletta. Swallowing, muscle power and functional tests, and swallowing quality of life report (SWAL-QOL) were assessed at baseline and after 24 weeks. Results: No serious drug-related adverse effects were noted. Time to swallow 80cc cold water (an OPMD validated dysphagia test) improved by 35.3[percnt\] (p

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Trehalose is a non-reducing disaccharide with two glucose molecules linked through an α, α-1,1-glucosidic bond. Trehalose has received attention for the past few decades for its role in neuroprotection especially in animal models of various neurodegenerative diseases, such as Parkinson and Huntington diseases. The mechanism underlying the neuroprotective effects of trehalose remains elusive. The prevailing hypothesis is that trehalose protects neurons by inducing autophagy, thereby clearing protein aggregates. Some of the animal studies showed activation of autophagy and reduced protein aggregates after trehalose administration in neurodegenerative disease models, seemingly supporting the autophagy induction hypothesis. However, results from cell studies have been less certain; although many studies claim that trehalose induces autophagy and reduces protein aggregates, the studies have their weaknesses, failing to provide sufficient evidence for the autophagy induction theory. Furthermore, a recent study with a thorough examination of autophagy flux showed that trehalose interfered with the flux from autophagosome to autolysosome, raising controversy on the direct effects of trehalose on autophagy. This review summarizes the fundamental properties of trehalose and the studies on its effects on neurodegenerative diseases. We also discuss the controversy related to the autophagy induction theory and seek to explain how trehalose works in neuroprotection.

Increased added sugar is contributing to a rise in aging-related diseases. Here, we use the nematode, Caenorhabditis elegans , which store sugar as both glycogen and trehalose. We demonstrate that by modifying sugar storage, we can prevent the harmful effects of a high-sugar diet. Our data show that a metabolic shift increasing the glucose disaccharide trehalose, and decreasing the glucose polysaccharide glycogen, extends lifespan and promotes healthy aging. The positive effects of trehalose require the DAF-16 transcription factor and the process of autophagy. Our data reveal the benefits of trehalose for prolonged health in the face of our high-sugar environment.

Stress granules (SGs) are an important component of cellular stress response. Compromised assembly of SGs as well as their premature or delayed disassembly affect physiology and survival of cells under stress or during recovery from stress. Consequently, abnormal turnover of SGs has been implicated in the development of various pathologies, including neurodegeneration. We found that pretreatment of cells with a natural disaccharide trehalose, a known autophagy enhancer, delays SG assembly and facilitates their premature post-stress disassembly. Mechanistically, the effect of trehalose on SGs is mediated via the p-eIF2α rather than autophagosome pathway. Trehalose increases pre-stress levels of p-eIF2α and its phosphatase subunits and promotes post-stress translational recovery. Upon prolonged treatment, trehalose impairs basal translation affecting production of transiently expressed proteins. Early translational recovery and SG disassembly induced by trehalose pretreatment can sensitise cells to stress and impair survival. Our study has important implications for the use of trehalose in studies of autophagic clearance of misfolded proteins and for targeting SGs as a possible therapeutic approach in neurodegenerative and other diseases.

Cellular homeostasis maintained by several cellular processes such as autophagy, apoptosis, inflammation, oxidative stress, aging, and neurodegenerati…

Diabetes mellitus is the most prevalent metabolic disorder contributing to significant morbidity and mortality in humans. Many preventative and therap…

Diabetes mellitus is the most prevalent metabolic disorder contributing to significant morbidity and mortality in humans. Many preventative and therapeutic agents have been developed for normalizing glycemic profile in patients with diabetes. In addition to various pharmacologic strategies, many non …

Fibrillar accumulation of A53T mutant α-synuclein (A53T-AS) in Lewy bodies is a symptom of Parkinsonism. Inhibitions of the overexpression and fibrillar aggregation of α-synuclein (AS) in vivo could be a promising strategy for treating Parkinson’s disease (PD). In this study, at concentrations lower than 1 mM, trehalose decreased the A53T-AS expression level in transduced PC12 cells. Although H2O2 and aluminum ions increased the expression level and neurotoxicity of A53T-AS in cells, proper trehalose concentrations inhibited the event. These studies adequately prove that trehalose at an appropriate dose would be potentially useful for PD treatment.

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

Neurodegenerative diseases characterized by aberrant accumulation of undigested cellular components represent unmet medical conditions for which the identification of actionable targets is urgently needed. Here we identify a pharmacologically actionable pathway that controls cellular clearance via A …

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