2016

Traumatic brain Injury (TBI) is a significant cause of death and long-term disability for which there are currently no effective pharmacological treatment options. In this study then, we utilized a mouse model of TBI to assess the therapeutic potential of the stable disaccharide trehalose, which is …

Machado-Joseph disease (MJD) is relatively prevalent among the Yemenite Jewish subpopulation living in Israel. Currently, there is no treatment able to modify the disease progression. Trehalose is a disaccharide with protein-stabilizing and autophagy-enhancing properties. In animal models of MJD, trehalose showed reduction of cerebellar lesion size and improved motor function. This study was designed to be a proof-of-concept, phase 2 study lasting 6 to 12 months, to determine the safety, tolerability, and efficacy of weekly IV administration of 15 g or 30 g 10% trehalose solution in 14 MJD patients. Primary endpoints were safety and tolerability, which were assessed by various clinical and laboratory tests. Secondary endpoints were changes in the Scale for Assessment and Rating of Ataxia (SARA) score, Neurological Examination Score for Spinocerebellar Ataxia (NESSCA), time to do 9-hole peg test (9HPT), time to do 8-meter walk (8MW), and quality of life assessed by the World Health Organization Quality-of-Life Questionnaire-BREF (WHOQoL-BREF). Trehalose was well tolerated, and no serious drug-related adverse events were noted. The average SARA score, NESSCA, and time to do 9HPT and 8MW and the WHOQoL-BREF for all patients remained stable at 6 months. Six patients received treatment for as long as 12 months and continued to remain stable on all the above tests. IV trehalose seems to be safe in humans and probably effective to stabilize neurological impairment in MJD.

Traumatic brain Injury (TBI) is a significant cause of death and long-term disability for which there are currently no effective pharmacological treatment options. In this study then, we utilized a mouse model of TBI to assess the therapeutic potential of the stable disaccharide trehalose, which is …

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, a disaccharide of glucose, is a naturally occurring nontoxic and nonreducing bioactive sugar. Trehalose is synthetized by many organisms when cells are exposed to stressful conditions, including dehydration, heat, oxidation, hypoxia or even anoxia. Although trehalose is not synthesized by …

In this work we investigate the role of CHIP in a new CHIP-mutation related ataxia and the therapeutic potential of trehalose. The patient's fibroblasts with a new form of hereditary ataxia, related to STUB1 gene (CHIP) mutations, and three age and sex-matched controls were treated with epoxomicin a …

Trehalose solution was an effective and safe eyedrop for the treatment of moderate to severe dry eye syndrome in this group of patients.

Trehalose is a natural disaccharide synthesized in various life forms, but not found in vertebrates. An increasing body of evidence demonstrates exceptional bioprotective characteristics of trehalose. This review discusses the scientific findings on potential ...

Methotrexate (MTX) is commonly used as a standard chemotherapy for many cancers, however its usage required high doses thereby leading to severe adverse effects. In a trial to find a suitable neoadjuvant therapy to decrease MTX dosage without lowering its chemotherapeutic efficacy, we investigated t …

Zinc (Zn) deficiency is a clinical consequence of brain injury that can result in neuropathological outcomes that are exacerbated with age. Here, we present laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging data showing modulation of brain Zn levels by the disaccharide trehalose

This study assessed the therapeutic utility of the autophagy enhancing stable disaccharide trehalose in the Tg2576 transgenic mouse model of Alzheimer's disease (AD) via an oral gavage of a 2% trehalose solution for 31 days. Furthermore, as AD is a neurodegenerative condition in which the transition …

The International Scientific Research Organization for Science, Engineering and Technology (ISROSET) is a Non-Profit Organization; The ISROSET is dedicated to improvement in academic sectors of Science (Chemistry, Bio-chemistry, Zoology, Botany, Biotechnology, Pharmaceutical Science, Bioscience, Bioinformatics, Biometrics, Biostatistics, Microbiology, Environmental Management, Medical Science, Forensic Science, Home Science, Library Science, Material Science Military Science, Physical Science, Physical Education Science, Educational Science, Fisheries, seed technology, Agriculture, Forestry Science, Mathematics, Physics, Statistics and Geology/Earth Science), Computer Science, Engineering and Information Technology, Commerce, Management, Economics Sociology and Social Science.

Brown seaweed is a common food for Asians, and the bioactive ingredient fucoxanthin exerts anti-apoptotic activities in several cell types. Renal tubu…

In this study, we observed that brown seaweed fucoidan inhibited human breast cancer progression by upregulating microRNA (miR)-29c and downregulating miR-17-5p, thereby suppressing their target genes, a disintegrin and metalloproteinase 12 (ADAM12) and ...

Random-pattern skin flaps are commonly used and valuable tools in reconstructive surgery, however, post-operative random skin flap necrosis remains a major and common complication. Previous studies have suggested that activating autophagy, a major pathway for degradation of intracellular waste, may improve flap survival. In this study, we investigated whether trehalose, a novel and potent autophagy activator, improves random skin flap viability. Our results demonstrated that trehalose significantly improves viability, augments blood flow, and decreases tissue edema. Furthermore, we found that trehalose leads to increased angiogenesis, decreased apoptosis, and reduced oxidative stress. Using immunohistochestry and western blot, we demonstrated that trehalose augments autophagy, and that inhibition of autophagy augmentation using 3MA significantly blunted the aforementioned benefits of trehalose therapy. Mechanistically, we showed that trehalose’s autophagy augmentation is mediated by activation and nuclear translocation of TFEB, which may be due to inhibition of Akt and activation of the AMPK-SKP2-CARM1 signaling pathway. Altogether, our results established that trehalose is a potent agent capable for significantly increasing random-pattern skin flap survival by augmenting autophagy and subsequently promoting angiogenesis, reducing oxidative stress, and inhibiting cell death.

This study assessed the therapeutic utility of the autophagy enhancing stable disaccharide trehalose in the Tg2576 transgenic mouse model of Alzheimer's disease (AD) via an oral gavage of a 2% trehalose solution for 31 days. Furthermore, as AD is a neurodegenerative condition in which the transition …

Biosciences, Biotechnology Research Asia is an international, open access, peer reviewed research journal covering all aspects of Biosciences and Biotechnology field.

(2017). Trehalose pathway as an antifungal target. Virulence: Vol. 8, New Antifungal Compounds, pp. 143-149.

Parkinson's disease is a debilitating neurodegenerative disorder that is pathologically characterized by intracellular inclusions comprised primarily of alpha-synuclein (αSyn) that can also be transmitted from neuron to neuron. Several lines of evidence suggest that these inclusions cause neurodegen …

ABSTRACT Objective: Micropropagation and elicitation studies of Aloe vera Methods: Standardisation of the regeneration protocol was done by using Murashige and Skoog (MS) media in combination with various plant growth regulators and elicitation studies were carried out by means of abiotic elicitors (salicylic acid, fructose and sodium chloride). Results: Direct regeneration through shoot tip gave the best response (0.2 mg/l Indole Butyric Acid (IBA) + 0.2mg/l 6-Benzylaminopurine (BAP)). Salicylic acid proved to be an effective abiotic elicitor, for suspension cultures of in vitro grown callus and also in vivo. It increased the content of polysaccharides, up to 7 times and phenolic compounds to almost 10 folds compared to untreated control kept under similar conditions. Conclusion: This study will make a path for the genetic transformation and metabolite enhancement along with their regulation, which can prove to be an asset towards pharmaceutical industry. Keywords: Aloe vera, Succulent plant, Micropropagation, Elicitation, Callus, Explant.

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 …

(2017). Trehalose as antifungal target: The picture is still incomplete. Virulence: Vol. 8, New Antifungal Compounds, pp. 237-238.

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.

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.

Trehalose, a non-reducing disaccharide, induces autophagy. Trehalose mitigates insulin resistance and adipocyte hypertrophy in obese mice; however, it…

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.