Trehalose has been studied and proven to have a beneficial effect on mammalian cells, an inhibitory effect on cell proliferation and a cytoprotective effect on cells exposed to UVB radiation (1).

Trehalose is a ubiquitous molecule found in lower and higher forms of life, but not in mammals. Until about 40 years ago, Trehalose was considered a storage molecule that promoted the release of glucose to perform cellular functions. This perception has recently changed substantially. The role of Trehalose has expanded, and this molecule is now being used in a variety of situations. Trehalose can be synthesised as a stress-sensitive factor when cells are exposed to environmental stresses such as heat, cold, oxidation, desiccation, and so on. When single-celled organisms are exposed to stress, they adapt by synthesising huge amounts of trehalose, which helps them maintain cellular integrity. In recent years, trehalose has proven useful for cryopreservation of sperm and stem cells and in the development of a highly reliable organ preservation solution (2).

Trehalose has suppressive effects on several pathological events, including vasospasm, inflammatory responses and lipid peroxidation (3) and, together with Bicaludamide, a new approach to the study of spinal and bulbar muscular atrophy (4).

In a growing immunocompromised population that is prone to invasive fungal infections, Trehalose possesses several important characteristics for the development of antifungal agents. First, it appears to have fungicidal characteristics and second, it is broad-spectrum and relevant against both ascomycetes and basidiomycetes species. Finally, it is not found in mammals so theoretically specific inhibitors of trehalose and its enzymes in fungi should be relatively non-toxic to mammals (5). 

Mo F, Zhou X, Yang M, Chen L, Tang Z, Wang C, Cui Y. Trehalose Attenuates Oxidative Stress and Endoplasmic Reticulum Stress-Mediated Apoptosis in IPEC-J2 Cells Subjected to Heat Stress. Animals (Basel). 2022 Aug 16;12(16):2093. doi: 10.3390/ani12162093. 

Abstract. This study was carried out to investigate the effects of trehalose (Tre) on antioxidant capacity, endoplasmic reticulum stress (ERS) response and apoptosis of heat-stressed intestinal porcine epithelial cells (IPEC-J2). IPEC-J2 cells were cultured at 37 °C until the end of the experiment (control, CON); exposed to heat stress for 2 h (43 °C, HS); or pretreated with 0.1, 1, 5, 10, and 15 mM trehalose at 37 °C for 4 h prior to heat stress exposure for 2 h. The optimum level of trehalose for protecting against HS-induced cell injuries was determined to be 10 mM, as evidenced by the highest cellular viability and lowest malondialdehyde (MDA) content and lactate dehydrogenase (LDH) activity. Based on these, IPEC-J2 cells were divided into three groups: the first group was cultured at 37 °C until the end of the experiment (control, CON); the second group was exposed to heat stress for 2 h (43 °C, HS); the third group was pretreated with 10 mM trehalose for 4 h at 37 °C prior to heat stress exposure for 2 h (Tre + HS). The reactive oxygen species (ROS) content, superoxide dismutase (SOD) activity, mitochondrial membrane potential (MMP) changes, and expressions of the manganese superoxide dismutase (SOD2), ERS and apoptosis-related proteins were determined. Compared to the CON group, HS significantly increased ROS generation (p < 0.01), decreased SOD activity (p < 0.05), and downregulated protein expression of SOD2 (p < 0.01). Compared to the HS group, Tre supplementation reduced ROS levels and increased SOD activity and SOD2 expression to the levels that were comparable to the control (p < 0.05). The HS-induced ERS response was evidenced by the increased protein expressions of glucose-regulated protein 78 (GRP78) (p < 0.01), eukaryotic translation initiation factor 2α (p-eif2α) (p < 0.01), transcription activator 4 (ATF4) (p < 0.01), and the protein expression of C/EBP homologous protein (CHOP) (p < 0.01), which were the four hallmarks of ERS. The Tre + HS group showed lower expressions of GRP78 (p < 0.01), p-eif2α (p < 0.01), ATF4 (p < 0.01), and CHOP (p < 0.01) than that of the HS group. Tre pretreatment attenuated HS-induced mitochondrial apoptosis in IPEC-J2 cells, demonstrated by the increased MMP and decreased proapoptotic proteins active caspase 3, Bax, and cytochrome c (Cyt c). Taken together, trehalose can protect against HS-induced oxidative damage and endoplasmic reticulum stress-mediated apoptosis in IPEC-J2 cells. These data may provide a nutritional strategy for alleviating heat stress in pig production.

Vinciguerra D, Gelb MB, Maynard HD. Synthesis and Application of Trehalose Materials. JACS Au. 2022 Jul 6;2(7):1561-1587. doi: 10.1021/jacsau.2c00309.

Abstract. Trehalose is a naturally occurring, nonreducing disaccharide that is widely used in the biopharmaceutical, food, and cosmetic industries due to its stabilizing and cryoprotective properties. Over the years, scientists have developed methodologies to synthesize linear polymers with trehalose units either in the polymer backbone or as pendant groups. These macromolecules provide unique properties and characteristics, which often outperform trehalose itself. Additionally, numerous reports have focused on the synthesis and formulation of materials based on trehalose, such as nanoparticles, hydrogels, and thermoset networks. Among many applications, these polymers and materials have been used as protein stabilizers, as gene delivery systems, and to prevent amyloid aggregate formation. In this Perspective, recent developments in the synthesis and application of trehalose-based linear polymers, hydrogels, and nanomaterials are discussed, with a focus on utilization in the biomedical field. © 2022 The Authors. Published by American Chemical Society.

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(1) Chen X, Li M, Li L, Xu S, Huang D, Ju M, Huang J, Chen K, Gu H. Trehalose, sucrose and raffinose are novel activators of autophagy in human keratinocytes through an mTOR-independent pathway. Sci Rep. 2016 Jun 22;6:28423. doi: 10.1038/srep28423.

(2) Jain NK, Roy I. Effect of trehalose on protein structure. Protein Sci. 2009 Jan;18(1):24-36. doi: 10.1002/pro.3. 

(3)  Echigo R, Shimohata N, Karatsu K, Yano F, Kayasuga-Kariya Y, Fujisawa A, Ohto T, Kita Y, Nakamura M, Suzuki S, Mochizuki M, Shimizu T, Chung UI, Sasaki N. Trehalose treatment suppresses inflammation, oxidative stress, and vasospasm induced by experimental subarachnoid hemorrhage. J Transl Med. 2012 Apr 30;10:80. doi: 10.1186/1479-5876-10-80.

(4) Giorgetti E, Rusmini P, Crippa V, Cristofani R, Boncoraglio A, Cicardi ME, Galbiati M, Poletti A. Synergic prodegradative activity of Bicalutamide and trehalose on the mutant androgen receptor responsible for spinal and bulbar muscular atrophy. Hum Mol Genet. 2015 Jan 1;24(1):64-75. doi: 10.1093/hmg/ddu419.

(5) Perfect JR, Tenor JL, Miao Y, Brennan RG. Trehalose pathway as an antifungal target. Virulence. 2017 Feb 17;8(2):143-149. doi: 10.1080/21505594.2016.1195529