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 ...
Trehalose-Induced Activation of Autophagy Improves Cardiac Remodeling After Myocardial Infarction
Trehalose (TRE) is a natural, nonreducing disaccharide synthesized by lower organisms. TRE exhibits an extraordinary ability to protect cells against …
Mystery solved Trehalose kickstarts autophagy by blocking glucose tran (...)
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).
Fibrillation of α-synuclein proceeds through distinct stages, with oligomers combining to form the seed or the nucleus, followed by exponential and saturation phases. Osmolytes are considered to act as protein stabilizers by virtue of their ability to inhibit protein aggregation. Trehalose, a non-re …
First Human Use of High Dose IV Trehalose Safety, Tolerability and Pha (...)
Objective: To demonstrate the safety and tolerability of repeated high dose IV administration of trehalose (Cabaletta) in OPMD patients, as part of a phase 2 therapy trial. Background: Trehalose is a disaccharide with protein stabilizing and autophagy enhancing properties. It showed efficacy in reducing abnormal protein aggregation in animal models of several human poly A- and poly Q- mediated hereditary neurological disorders (of which OPMD is an example). Design and Methods: Eleven patients with molecularly confirmed OPMD (age: mean 63 years, range 43-78; disease duration: mean 10.6 years, range 1-24) received weekly infusion of 30 gr Cabaletta for 9-16 weeks (at time of abstract submission). Results: No drug-related adverse effects were noted, in particular no cardiovascular changes were observed. A subtle increase (mean= 5 mg[percnt]) in plasma glucose concentrations was observed 1 hour after trehalose administration. No increase in insulin levels was found. Short term glycosuria was recorded, probably due to trehalase activity in the kidney. Levels of plasma trehalose after a single administration in humans reached the expected concentrations determined in the animal studies as necessary for intracellular activity of trehalose (max. levels of 1000-2000 mgr/mL after 1 hour) and were retained up to 5 hours. Conclusions: Based on these preliminary findings, high dose IV trehalose (Cabaletta) is safe in humans. Clinical trials in OPMD and spinocerebellar atrophy type 3 are currently going on. More disorders with similar PolyA/Poly Q genotypic changes may be suitable for such trials. Disclosure: Dr. Argov has received personal compensation for activities with BioBlast Pharma as chief medical officer. Dr. Vornovitsky has nothing to disclose. Dr. Blumen has received personal compensation for activities with Bioblast Pharma as a consultant. Dr. Caraco has received personal compensation for activities with Sanofi, NeuroDerm, and Roche as a consultant. Thursday, April 23 2015, 2:00 pm-6:30 pm
Trehalose Improves Cognition in the Transgenic Tg2576 Mouse Model of Alzheimer's Disease. - PubMed - NCBI
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 …
Trehalose Improves Cognition in the Transgenic Tg2576 Mouse Model of A (...)
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 …
Focus Drug Development Variable Effects of Autophagy Induction by Treh (...)
Trehalose is a non-reducing sugar formed from two glucose units. Trehalose induces abundant autophagy in cultured cells and also reduces the rate of aggregation of the huntingtin protein in the animal model of Huntington disease, a chronic neurological ...
Trehalose improves human fibroblast deficits in a new CHIP-mutation re (...)
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 …
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 …
Formation of Stable Nanobubbles on Reconstituting Lyophilized Formulat (...)
During an investigation of subvisible particles found in lyophilized formulations of intravenous immunoglobulin, we used resonant mass measurement tec…
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 …
Trehalose in Machado-Joseph Disease Safety, Tolerability, and Efficacy SpringerLink
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.
Frontiers Potential Fast COVID-19 Containment With Trehalose Immunology
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.
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 …
Trehalose induced antidepressant-like effects and autophagy enhancemen (...)
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.
Frontiers Trehalose May Decrease the Transmission of Zika Virus to th (...)
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...
Trehalose induced conformational changes in the amyloid-ß peptide. - P (...)
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 …
Trehalose Induces Autophagy Against Inflammation by Activating TFEB Signaling Pathway in Human Corneal Epithelial Cells Exposed to Hyperosmotic Stress - PubMed
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.
Full article A head-to-head comparison review of biological and toxicological studies of isomaltulose, d-tagatose, and trehalose on glycemic control
(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.
Trehalose induces functionally active conformation in the intrinsicall (...)
(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.
Trehalose inhibits cell proliferation and amplifies long-term temozolomide- and radiation-induced cytotoxicity in melanoma cells A role for autoph... - PubMed - NCBI
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 …
Glycemic, insulinemic and incretin responses after oral trehalose ingestion in healthy subjects. - PubMed - NCBI
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.
Trehalose inhibits cell proliferation and amplifies long-term temozolomide- and radiation-induced cytotoxicity in melanoma cells A role for autophagy and premature senescence
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 ...
Trehalose inhibits H2O2-induced autophagic death in dopaminergic SH-SY5Y cells via mitigation of ROS-dependent endoplasmic reticulum stress and AMP... - PubMed - NCBI
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 …
Growth Inhibition by Novel Liposomes Including Trehalose Surfactant Ag (...)
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.
Trehalose inhibits H2O2-induced autophagic death in dopaminergic SH-SY5Y cells via mitigation of ROS-dependent endoplasmic reticulum stress and AMPK activation
Trehalose Inhibits Human Immunodeficiency Virus Type 1 Infection in Primary Human Macrophages and CD4 + T Lymphocytes through Two Distinct Mechanisms - PubMed
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 …
Honey, trehalose and erythritol as sucrose-alternative sweeteners for (...)
The use of sucrose-alternative sweeteners in ice cream production could satisfy requirements of modern consumers focused on natural and nutritionally …
