Trehalose

The accumulation of misfolded α-synuclein in dopamine (DA) neurons is believed to be of major importance in the pathogenesis of Parkinson's disease (PD). Animal models of PD, based on viral-vector-mediated over-expression of α-synuclein, have been developed and show evidence of dopaminergic toxicity …

Background Trehalose is well known as a functional disaccharide with anti-metabolic activities such as suppression of adipocyte hypertrophy in mice and alleviation of impaired glucose tolerance in humans. Recently, a new type of adipocyte beige cells, involved in so-called white adipocyte tissue (WAT) browning, has received much attention as a target for adaptive thermogenesis. To clarify the relationship between adipocyte hypertrophy suppression and beige cells involved in thermogenesis, we examined the effect of trehalose on the changes in beige adipocytes in mice under normal dietary conditions. Methods Mice fed a normal diet were administered water containing 0.3% (W/V) trehalose for 16 weeks, 0.3% (W/V) maltose, or water without saccharide (controls). Body temperature and non-fasting blood glucose levels were measured every 3 weeks. After 16 weeks of these treatments, mesenteric and inguinal adipose tissues were collected for measuring adipocyte size, counting the number of UCP1 positive cells by image analysis, and preparing mRNA to analyze beige adipocyte-related gene expression. Results Mice administered a continuous intake of trehalose exhibited a thermogenic ability as represented by an increase in rectal temperature, which was maintained at a relatively high level from 3 to 9 weeks and was significantly higher at 15 weeks in comparison with that of the maltose group. In addition to the reduced hypertrophy of mesenteric and inguinal adipose tissues, the trehalose group showed a significant increase in the rates of beige adipocytes in each WAT in comparison with those of the maltose and the water groups. Interestingly, a negative correlation was found between the mean cell sizes of adipocytes and the rates of beige adipocytes in the WAT. Furthermore, real-time PCR showed that the expression of Cidea and Ucp1 mRNAs, which are markers for beige adipocytes in the inguinal adipose tissue, increased in the trehalose group. Conclusions Continuous administration of trehalose to mice fed a normal diet induced WAT browning accompanied by suppression of white adipocyte hypertrophy, elevated body temperature and decreased blood glucose levels, which resulted in enhancement of energy metabolism. Therefore, we propose trehalose as a new type of thermogenic dietary component to prevent obesity by promoting WAT browning.

Trehalose is a sugar which, on a cellular level, appears to have therapeutic mechanisms by regulating protein unfolding. Practically, its low oral absorption in its intact form paired with rapid digestion may preclude any benefits of oral intake.

Background Trehalose is a natural disaccharide that is widely distributed. A previous study has shown that daily consumption of 10 g of trehalose improves glucose tolerance in individuals with signs of metabolic syndrome. In the present study, we determined whether a lower dose (3.3 g/day) of trehalose improves glucose tolerance in healthy Japanese volunteers. Methods This was a randomized, double-blind, placebo-controlled study of healthy Japanese participants (n = 50). Each consumed 3.3 g of trehalose (n = 25) or sucrose (n = 25) daily for 78 days. Their body compositions were assessed following 0, 4, 8, and 12 weeks; and serum biochemical parameters were assayed and oral 75-g glucose tolerance tests were performed at baseline and after 12 weeks. Results There were similar changes in body composition and serum biochemistry consistent with established seasonal variations in both groups, but there were no differences in any of these parameters between the two groups. However, whereas after 12 weeks of sucrose consumption, the plasma glucose concentration 2 h after a 75-g glucose load was significantly higher than the fasting concentration, after 12 weeks of trehalose consumption the fasting and 2-h plasma glucose concentrations were similar. Furthermore, an analysis of the participants with relatively high postprandial blood glucose showed that the plasma glucose concentration 2 h after a 75-g glucose load was significantly lower in the trehalose group than in the sucrose group. Conclusions Our findings suggest that trehalose helps lower postprandial blood glucose in healthy humans with higher postprandial glucose levels within the normal range, and may therefore contribute to the prevention of pathologies that are predisposed to by postprandial hyperglycemia,, even if the daily intake of trehalose is only 3.3 g, an amount that is easily incorporated into a meal. Trial registration UMIN, UMIN000033536 . Registered 27 July 2018.

This paper contains a review of the history, natural occurrence, human consumption, metabolism, manufacture, and the results of eight standardized animal safety studies using trehalose. Trehalose (alpha,alpha-trehalose) is a naturally occurring sugar containing two D-glucose units in an alpha,alpha- …

Serine protease inhibitors (serpins) family have a complex mechanism of inhibition that requires a large scale conformational change. Antithrombin (AT), a member of serpin superfamily serves as a key regulator of the blood coagulation cascade, deficiency of which leads to thrombosis. In recent years …

Aim Endoplasmic reticulum stress is associated with the pathophysiology of various liver diseases. Endoplasmic reticulum stress mediates the accumulation of abnormal proteins and leads to oxidative ...

Aim of this study was to characterize the effects of oral trehalose administration (2%w/v) on healthspan in old mice. Trehalose was administered in dr…

Accelerating the clearance of intracellular protein aggregates through elevation of autophagy represents a viable approach for the treatment of neurodegenerative diseases. In our earlier report, we have demonstrated the enhanced degradation of mutant huntingtin protein aggregates through autophagy p …

Abnormal accumulation of amyloid proteins is linked to neuronal degeneration in Alzheimer's disease brains, driving cognitive decline. Disruption of autophagy pathway contributes to the development o...

Cadmium (Cd) is a persistent environmental contaminant and induces neurotoxicity in animals. Trehalose (Tre) exhibits powerful neuroprotective effects in certain brain injury models. Herein, we revealed the specific molecular mechanism underlying the protective effects of Tre against Cd-induced brain damage

The HT-29 human adenocarcinoma cell line has been used extensively in the study of colonic cell differentiation and colon cancer. We report here that substitution of glucose with trehalose (alpha-D-glucopyranosyl-alpha-D-glucopyranoside) depresses growth and promotes mucin-producing, goblet-like mat …

Background Machado–Joseph disease (MJD), also known as spinocerebellar ataxia type 3, is the most common of the dominantly inherited ataxias worldwide and is characterized by mutant ataxin-3 aggregation and neuronal degeneration. There is no treatment available to block or delay disease progression. In this work we investigated whether trehalose, a natural occurring disaccharide widely used in food and cosmetic industry, would rescue biochemical, behavioral and neuropathological features of an in vitro and of a severe MJD transgenic mouse model. Methods Two MJD animal models, a lentiviral based and a transgenic model, were orally treated with 2% trehalose solution for a period of 4 and 30 weeks, respectively. Motor behavior (rotarod, grip strength and footprint patterns) was evaluated at different time points and neuropathological features were evaluated upon in-life phase termination. Results Trehalose-treated MJD mice equilibrated for a longer time in the rotarod apparatus and exhibited an improvement of ataxic gait in footprint analysis. Trehalose-mediated improvements in motor behaviour were associated with a reduction of the MJD-associated neuropathology, as MJD transgenic mice treated with trehalose presented preservation of cerebellar layers thickness and a decrease in the size of ataxin-3 aggregates in Purkinje cells. In agreement, an improvement of neuropathological features was also observed in the full length lentiviral-based mouse model of MJD submitted to 2% trehalose treatment. Conclusions The present study suggests trehalose as a safety pharmacological strategy to counteract MJD-associated behavioural and neuropathological impairments.

The disaccharide trehalose is commonly considered to stimulate autophagy. Cell treatment with trehalose could decrease cytosolic aggregates of potentially pathogenic proteins, including mutant huntingtin, α-synuclein, and phosphorylated tau that are associated with neurodegenerative diseases. Here, …

This work aimed to determine the effect of homogenization pressures and addition of trehalose on the functional properties of mandarin juice enriched …

The disaccharide trehalose is commonly considered to stimulate autophagy. Cell treatment with trehalose could decrease cytosolic aggregates of potentially pathogenic proteins, including mutant huntingtin, α-synuclein, and phosphorylated tau that are associated with neurodegenerative diseases. Here, …

The disaccharide trehalose is commonly considered to stimulate autophagy. Cell treatment with trehalose could decrease cytosolic aggregates of potentially pathogenic proteins, including mutant huntingtin, α-synuclein, and phosphorylated tau that are associated with neurodegenerative diseases. Here, …

Purpose. This randomized, observer-masked, crossover study investigated the effect of two hyaluronic acid/trehalose-based containing formulations, with different physical properties, on the signs and symptoms in patients with moderate to severe dry eye disease (DED). Methods. In one group, patients received a mixture of sodium hyaluronate and trehalose (HT, Thealoz Duo®) for use during the day. In the other group, patients received a more viscous formulation consisting of hyaluronic acid, trehalose, and carbomer (HTC-gel, Thealoz Duo Gel) to use pro re nata. Both groups used HTC-gel before going to bed. Clinical standard tests for DED were performed at the beginning and end of each one-week period. Further, patient satisfaction including quality of sleep was assessed using a visual analogue scale. Results. Corneal fluorescein and conjunctival lissamine green staining scores decreased, and tear breakup time (BUT) increased for both groups ( each). Mean instillation frequency was 3.1 ± 2.6 drops/day when using HT and 1.9 ± 2.2 drops/day when using HTC-gel (). A significant improvement in the quality of sleep was observed with both treatments (). Conclusions. Our results show improvement in signs and symptoms of DED in both groups. While instillation of HTC-gel resulted in a lower instillation frequency, both formulations of trehalose showed good clinical efficacy. This trial is registered with NCT02980913.

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Oxidative stress-related apoptosis and autophagy play crucial roles in the development of osteoarthritis (OA), a progressive cartilage degenerative disease with multifactorial etiologies. Here, we determined autophagic flux changes and apoptosis in human OA and tert-Butyl hydroperoxide (TBHP)-treate …

Peritoneal fibrosis (PF) is a severe complication of peritoneal dialysis, but there are few effective therapies for it. Recent studies have revealed a new biological function of trehalose as an autophagy inducer. Thus far, there are few reports regarding the therapeutic effects of trehalose on fibrotic diseases. Therefore, we examined whether trehalose has anti-fibrotic effects on PF. PF was induced by intraperitoneal injection of chlorhexidine gluconate (CG). CG challenges induced the increase of peritoneal thickness, ColIα1 mRNA expression and hydroxyproline content, all of which were significantly attenuated by trehalose. In addition, CG challenges induced a marked peritoneal accumulation of α-SMA+ myofibroblasts that was reduced by trehalose. The number of Wt1+ α-SMA+ cells in the peritoneum increased following CG challenges, suggesting that a part of α-SMA+ myofibroblasts were derived from peritoneal mesothelial cells (PMCs). The number of Wt1+ α-SMA+ cells was also suppressed by trehalose. Additionally, trehalose attenuated the increase of α-SMA and ColIα1 mRNA expression induced by TGF-β1 through Snail protein degradation, which was dependent on autophagy in PMCs. These results suggest that trehalose might be a novel therapeutic agent for PF through the induction of autophagy and the suppression of mesothelial-to-mesenchymal transition in PMCs.

Lafora disease (LD) is one of the progressive and fatal forms of a neurodegenerative disorder and is characterized by teenage-onset myoclonic seizures. Neuropathological changes in LD include the formation of abnormal glycogen as Lafora bodies, gliosis, and neuroinflammation. LD is caused by defects in the gene coding for phosphatase (laforin) or ubiquitin ligase (malin). Mouse models of LD, developed by targeted disruption of these two genes, develop most symptoms of LD and show increased susceptibility to induced seizures. Studies on mouse models also suggest that defective autophagy might contribute to LD etiology. In an attempt to understand the specific role of autophagy in LD pathogenesis, in this study, we fed LD animals with trehalose, an inducer of autophagy, for 3 months and looked at its effect on the neuropathology and seizure susceptibility. We demonstrate here that trehalose ameliorates gliosis, neuroinflammation, and endoplasmic reticulum stress and reduces susceptibility to induced seizures in LD animals. However, trehalose did not affect the formation of Lafora bodies, suggesting the epileptic phenotype in LD could be either secondary to or independent of Lafora bodies. Taken together, our results suggest that autophagy inducers can be considered as potential therapeutic molecules for Lafora disease.

Background: Chondroitin sulfate proteoglycans (CSPGs) are the major cause of axonal regeneration failure at the site of lesion in spinal cord injury (SCI). Inflammation is believed to stimulate the upregulation of CSPGs expression. Recent evidence showed that trehalose reduces the development of inflammation in SCI. The aim of this study was to investigate the effect of trehalose on neurocan and Neural-Glial Antigen 2 (NG2) mRNA levels in SCI in rats. Methods: In this experimental study, male rats were divided into six groups (n=15). Sham (laminectomy), SCI (laminectomy and SCI), vehicle (laminectomy and SCI, treated with phosphate buffer saline), and T10, T100 and T1000 (laminectomy and SCI, treated with 10, 100 and 1000 mM trehalose). Five rats in each group were sacrificed at 1, 3 and 7 days post-injury to measure neurocan and NG2 mRNA levels in lesion. Statistical analysis was performed using Kruskal-Wallis methods followed by the Mann-Whitney test. Results: Findings indicated that SCI upregulated neurocan and NG2 mRNA levels at all times. No significant difference was observed in neurocan and NG2 gene transcripts between SCI and vehicle groups (p>0.05). However, 10 mM trehalose downregulated the mRNA level of both neurocan (0.76 and 0.65 fold) and NG2 (0.75 and 0.70 fold) at 3 and 7 days post-SCI compared to vehicle group (p p

Many degenerative disorder such as Parkinsons, Alzheimers, Huntingtons disease, etc are caused due to the deposition of amyloid fibrils, formed due to the ordered aggregation of misfolded/unfolded proteins. Misfolded or unfolded proteins aggregate mostly through hydrophobic interactions which are unexposed in native state, but become exposed upon unfolding. To counteract amyloid related diseases, inhibition of the protein self assembly into fibril is a potential therapeutic strategy. The study aims at investigating the effect of selected compounds, namely trehalose and magnesium chloride hexahydrate towards inhibition and disaggregation of amyloid fibrils using Hen Egg White Lysozyme as a model. We further attempted to understand the mechanism of action with the help of various biophysical, microscopic as well as computational studies. A common mechanism of action was identified where the selected compounds exert their anti-amyloidogenic effects by altering HEWL conformations characterized by reduction in the beta sheet content and decrease in exposed hydrophobic surfaces. The altered conformation seems to have lesser amyloidogenic propensity leading to inhibition as well as disaggregation of amyloids.

Parkinson's disease (PD) is a progressive movement disorder resulting primarily from loss of nigrostriatal dopaminergic neurons. PD is characterized by the accumulation of protein aggregates, and evidence suggests that aberrant protein deposition in dopaminergic neurons could be related to the dysre …

Trehalose (TRE), a disaccharide, is absorbed slowly and gradually increases the blood glucose (GLU) level along with reducing insulin secretion. The aim of this study was twofold. First, we examined exercise performance following ingestions of either GLU, TRE, or water (WAT). The second purpose was …