Trehalose: a review of properties, history of use and human tolerance, and results of multiple safety studies

Richards, A.; Krakowka, Steven; Dexter, L.B; Schmid, Heide; Wolterbeek, A.P.M.; Waalkens-Berendsen, D.H.; Shigoyuki, A; Kurimoto, Masashi

doi:10.1016/s0278-6915(02)00011-x

Cited by 495 publications

(379 citation statements)

References 102 publications

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“…5(a)) as discussed earlier. The decrease in the water sorption may be explained by the replacement of strongly immobilized water in the polymer chains by trehalose and is in accordance with the low hygroscopic nature of the molecule itself [53]. The exact same behaviour was verified for F NH and F NT , suggesting that Hydrovance has only a significant influence (P < 0.05) at very high RH in the increase of the water content while trehalose induces a decrease of the water content at 75% RH.…”

Section: Water Sorption (%)supporting

confidence: 68%

Films based on chitosan polyelectrolyte complexes for skin drug delivery: Development and characterization

Silva

Pereira

Ramalho

et al. 2008

Journal of Membrane Science

116

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a b s t r a c tNovel chitosan based polyelectrolyte complexes (PEC) were developed and optimized in order to obtain films possessing the optimal functional properties (flexibility, resistance, water vapour transmission rate and bioadhesion) to be applied on skin. The development was based on the combination of chitosan and two polyacrylic acid (PAA) polymers with different crosslinkers and crosslinking densities. The interaction between the polymers was maximized controlling the pH, and by forming the films at a pH value close to the pK a of the respective components as identified by potentiometric and turbidimetric titrations. The action of glycerol, PEG200, Hydrovance and trehalose upon the functional properties of the films was also evaluated. Glycerol was found to improve the film properties in terms of flexibility, resistance and water vapour transmission rate (WVTR) with a maximum effect at 30%. The application of a pressure sensitive adhesive (PSA) significantly improved bioadhesion with a negligible influence in the resistance and flexibility of the films.The optimized film, including adhesive, has shown very good properties for application in the skin and represents a very promising formulation for further incorporation of drugs for topical and transdermal administration.

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Section: Water Sorption (%)supporting

confidence: 68%

Films based on chitosan polyelectrolyte complexes for skin drug delivery: Development and characterization

Silva

Pereira

Ramalho

et al. 2008

Journal of Membrane Science

116

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“…Thus, if appropriately stimulated, neurons can restore the clearance of intralysosomal material even in the absence of catabolic enzymes, most likely through processes such as lysosomal exocytosis [19]. It is noteworthy that possible therapeutic applications of trehalose may be challenged by the presence of trehalase, a specific trehalose-degrading enzyme, in the intestine, kidney, and other organs in mammals [66]. It remains to be investigated if the protective effects observed upon trehalose oral administration are entirely due to direct exposure of the trehalose fraction that is able to reach the brain or if additional, secondary pathways possibly triggered by dietary trehalose may also play a protective role.…”

Section: Discussionmentioning

confidence: 99%

Trehalose reduces retinal degeneration, neuroinflammation and storage burden caused by a lysosomal hydrolase deficiency

et al. 2018

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The accumulation of undegraded molecular material leads to progressive neurodegeneration in a number of lysosomal storage disorders (LSDs) that are caused by functional deficiencies of lysosomal hydrolases. To determine whether inducing macroautophagy/autophagy via small-molecule therapy would be effective for neuropathic LSDs due to enzyme deficiency, we treated a mouse model of mucopolysaccharidosis IIIB (MPS IIIB), a storage disorder caused by deficiency of the enzyme NAGLU (alpha-N-acetylglucosaminidase [Sanfilippo disease IIIB]), with the autophagy-inducing compound trehalose. Treated naglu–/ – mice lived longer, displayed less hyperactivity and anxiety, retained their vision (and retinal photoreceptors), and showed reduced inflammation in the brain and retina. Treated mice also showed improved clearance of autophagic vacuoles in neuronal and glial cells, accompanied by activation of the TFEB transcriptional network that controls lysosomal biogenesis and autophagic flux. Therefore, small-molecule-induced autophagy enhancement can improve the neurological symptoms associated with a lysosomal enzyme deficiency and could provide a viable therapeutic approach to neuropathic LSDs.Abbreviations: ANOVA: analysis of variance; Atg7: autophagy related 7; AV: autophagic vacuoles; CD68: cd68 antigen; ERG: electroretinogram; ERT: enzyme replacement therapy; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFAP: glial fibrillary acidic protein; GNAT2: guanine nucleotide binding protein, alpha transducing 2; HSCT: hematopoietic stem cell transplantation; INL: inner nuclear layer; LC3: microtubule-associated protein 1 light chain 3 alpha; MPS: mucopolysaccharidoses; NAGLU: alpha-N-acetylglucosaminidase (Sanfilippo disease IIIB); ONL: outer nuclear layer; PBS: phosphate-buffered saline; PRKCA/PKCα: protein kinase C, alpha; S1BF: somatosensory cortex; SQSTM1: sequestosome 1; TEM: transmission electron microscopy; TFEB: transcription factor EB; VMP/VPL: ventral posterior nuclei of the thalamus

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“…In summary, our data suggest that trehalose may be applicable to the treatment of various other neurodegenerative diseases in addition to SCA14. Trehalose is widely used in foods as a sweetener and in cosmetics as a humectant; thus its safety has already been established (40). We expect that trehalose has the potential to become a useful drug for treatment of neurodegenerative diseases, including SCA14.…”

Section: Pcmentioning

confidence: 99%

Effect of Trehalose on the Properties of Mutant γPKC, Which Causes Spinocerebellar Ataxia Type 14, in Neuronal Cell Lines and Cultured Purkinje Cells*

Seki

Abe-Seki

Kikawada

et al. 2010

Journal of Biological Chemistry

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Several missense mutations in the protein kinase C␥ (␥PKC) gene have been found to cause spinocerebellar ataxia type 14 (SCA14), an autosomal dominant neurodegenerative disease. We previously demonstrated that the mutant ␥PKC found in SCA14 is susceptible to aggregation, which induces apoptotic cell death. The disaccharide trehalose has been reported to inhibit aggregate formation and to alleviate symptoms in cellular and animal models of Huntington disease, Alzheimer disease, and prion disease. Here, we show that trehalose can be incorporated into SH-SY5Y cells and reduces the aggregation of mutant ␥PKC-GFP, thereby inhibiting apoptotic cell death in SH-SY5Y cells and primary cultured Purkinje cells (PCs). Trehalose acts by directly stabilizing the conformation of mutant ␥PKC without affecting protein turnover. Trehalose was also found to alleviate the improper development of dendrites in PCs expressing mutant ␥PKC-GFP without aggregates but not in PCs with aggregates. In PCs without aggregates, trehalose improves the mobility and translocation of mutant ␥PKC-GFP, probably by inhibiting oligomerization and thereby alleviating the improper development of dendrites. These results suggest that trehalose counteracts various cellular dysfunctions that are triggered by mutant ␥PKC in both neuronal cell lines and primary cultured PCs by inhibiting oligomerization and aggregation of mutant ␥PKC.

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Trehalose: a review of properties, history of use and human tolerance, and results of multiple safety studies

Cited by 495 publications

References 102 publications

Films based on chitosan polyelectrolyte complexes for skin drug delivery: Development and characterization

Films based on chitosan polyelectrolyte complexes for skin drug delivery: Development and characterization

Trehalose reduces retinal degeneration, neuroinflammation and storage burden caused by a lysosomal hydrolase deficiency

Effect of Trehalose on the Properties of Mutant γPKC, Which Causes Spinocerebellar Ataxia Type 14, in Neuronal Cell Lines and Cultured Purkinje Cells*

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