Trehalose

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

Although vertebrates cannot synthesize the natural disaccharide trehalose, exogenous administration of trehalose to mammalian cells may be beneficial for protein misfolding disorders. In this issue, DeBosch et al . show that trehalose may also be useful in treating nonalcoholic fatty liver disease and identify inhibition of cellular glucose import through SLC2A (also known as GLUT) transporters as a mechanism by which trehalose stimulates autophagy through the adenosine monophosphate–activated protein kinase (AMPK).

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 …

New research shows that a natural sugar called trehalose prevents fatty liver disease in mice. The study found that trehalose prevents the sugar fructose -- thought to be a major contributor to nonalcoholic fatty liver disease -- from entering the liver and triggers a cellular housekeeping process that cleans up excess fat buildup inside liver cells.

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

Abstract. Trehalose is a nonreducing disaccharide in which the two glucose units are linked in an α,α-1,1-glycosidic linkage. This sugar is present in a wide va

Autophagy impairment has been demonstrated in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) and could be a new target of treatment. Trehalose is a natural, nonreducing disaccharide that has been shown to enhance autophagy. Therefore, we investigated whether trehalose treatment reduces renal cyst formation in a Pkd1-hypomorphic mouse model. Pkd1 miRNA transgenic (Pkd1 miR Tg) mice and wild-type littermates were given drinking water supplemented with 2% trehalose from postnatal day 35 to postnatal day 91. The control groups received pure water or 2% sucrose for the control of hyperosmolarity. The effect on kidney weights, cystic indices, renal function, cell proliferation, and autophagic activities was determined. We found that Pkd1 miR Tg mice had a significantly lower renal mRNA expression of autophagy-related genes, including atg5, atg12, ulk1, beclin1, and p62, compared with wild-type control mice. Furthermore, immunohistochemical analysis showed that cystic lining cells had strong positive staining for the p62 protein, indicating impaired degradation of the protein by the autophagy-lysosome pathway. However, trehalose treatment did not improve reduced autophagy activities, nor did it reduce relative kidney weights, plasma blood urea nitrogen levels, or cystatin C levels in Pkd1 miR Tg mice. Histomorphological analysis revealed no significant differences in the renal cyst index, fibrosis score, or proliferative score among trehalose-, sucrose-, and water-treated groups. Our results demonstrate that adding trehalose to drinking water does not modulate autophagy activities and renal cystogenesis in Pkd1-deficient mice, suggesting that an oral supplement of trehalose may not affect the progression of ADPKD.

Trehalose increases blood glucose levels slowly and induces a slight insulin response. The present study aimed to study the effect of trehalose on prolonged exercise performance. The participants were 12 healthy men (age: 21.3 ± 0.9 y). After an overnight fast (12 h), they first exercised with a constant load (intensity: 40% V˙O2peak) for 60 min using a bicycle ergometer. They continued to exercise with a constant load (40% V˙O2peak) for 30 min between four sets of the 30-s Wingate test. After the 1st set, each participant ingested 500 mL water (control), 8% glucose, or 8% trehalose in three trials. These three trials were at least one week apart and were conducted in a double-blind and randomized crossover manner. Blood was collected for seven biochemical parameters at 12 time points during the experiment. The area under the curve of adrenaline after ingestion of trehalose was significantly lower than that for water and tended to be lower than that for glucose in the later stage of the exercise. Lower secretion of adrenaline after a single dose of 8% trehalose during prolonged exercise reflected the preservation of carbohydrates in the body in the later stage of the exercise. In conclusion, a single ingestion of trehalose helped to maintain prolonged exercise performance.

We hypothesized that supplementation with trehalose, a disaccharide that reverses arterial aging in mice, would improve vascular function in middle-aged and older (MA/O) men and women. Thirty-two healthy adults aged 50-77 years consumed 100 g/day of trehalose ...

We hypothesized that supplementation with trehalose, a disaccharide that reverses arterial aging in mice, would improve vascular function in middle-aged and older (MA/O) men and women. Thirty-two healthy adults aged 50-77 years consumed 100 g/day of trehalose (n=15) or maltose (n=17, isocaloric cont …

We hypothesized that supplementation with trehalose, a disaccharide that reverses arterial aging in mice, would improve vascular function in middle-aged and older (MA/O) men and women. Thirty-two healthy adults aged 50-77 years consumed 100 g/day of trehalose ...

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 rapid …

A total of 10 male collegiate distance runners participated in a randomized crossover trial. After completing a warm-up, each participant ingested 300 mL of a t...

Sugars are well known to retain protein structures and to protect denaturation. Protective actions of sugars on protein structures have been discussed…

Disaccharide glasses are increasingly used to immobilize proteins at room temperature for structural/functional studies and long-term preservation. To unravel the molecular basis of protein immobilization, we studied the effect of sugar/protein concentration ratios in trehalose or sucrose matrixes, in which the bacterial photosynthetic reaction center (RC) was embedded as a model protein. The structural, dynamical, and H-bonding characteristics of the sugar–protein systems were probed by high-field W-band EPR of a matrix-dissolved nitroxide radical. We discovered that RC immobilization and thermal stabilization, being independent of the protein concentration in trehalose, occur in sucrose only at sufficiently low sugar/protein ratios. EPR reveals that only under such conditions does sucrose form a microscopically homogeneous matrix that immobilizes, via H-bonds, the nitroxide probe. We conclude that the protein immobilization capability depends critically on the propensity of the glass-forming sugar to create intermolecular H-bond networks, thus establishing long-range, homogeneous connectivity within the matrix.

We explored whether the combination of anti-oxidant and anti-inflammatory guava (Psidium guajava) and trehalose treatment protects the kidney and pancreas against Type II diabetes (T2DM)-induced injury in rats. We measured the active component of guava juice by HPLC analysis. T2DM was induced in Wis …

We explored whether the combination of anti-oxidant and anti-inflammatory guava (Psidium guajava) and trehalose treatment protects the kidney and pancreas against Type II diabetes (T2DM)-induced injury in rats. We measured the active component of guava juice by HPLC analysis. T2DM was induced in Wis …

PURPOSE: To compare the therapeutic effect of sodium hyaluronate (SH)–trehalose (Trehalube, Microlabs, Bangalore, India, SH 0.1% and trehalose 3%) or SH (0.1% Hylotears, Raymed, Chandigarh, India) alone in patients with dry eye disease (DED).MATERIALS AND METHODS: Patients were randomized into two groups: SH-trehalose (SH 0.1% and trehalose 3%) or SH (0.1% Hylotears) alone. The Ocular Surface Disease Index (OSDI) questionnaire was used to assess patient's symptoms. Patients were followed up at 4 and 8 weeks, and OSDI score, tear film break-up time (TBUT), tear film height (TFH), Schirmer's test, and conjunctival staining were evaluated at each visit.RESULTS: A total of 384 patients were included in the study, 192 patients in each arm. The mean age of participants was 37.62 + 14.4 years and 225 were women (56%). The improvement in Schirmer's test was significantly better in the SH-trehalose group at 8 weeks (5.26 + 4.3 mm, 95% confidence interval = 4.6–5.9 mm) compared to the SH group (3.71 + 3.9, 95% confidence interval = 3.15–4.28 mm). The TBUT and TFH showed slight improvement at 4 weeks in both groups, but not at 8 weeks. There were no group differences at all-time points in terms of conjunctival staining and OSDI-based grades of DED.CONCLUSION: It was found that treating dry eye with SH-trehalose leads to greater improvement in the Schirmer's values and TBUT after 8 weeks of sustained use in patients with DED, and this was more pronounced in those with severe DED.

The half-lives for spontaneous hydrolysis of trehalose and sucrose at 25 °C are 6.6 × 10[6] years and 440 years. The half-lives for decomposition of the hydrolysis products glucose and fructose are 96 years and 70 days, respectively. ...