Trehalose (hydrate) is a natural, safe, non-specific disaccharide osmoprotectant[1]. Trehalose (hydrate) exerts anti-desiccation, anti-freezing, and anti-oxidative effects by stabilizing protein and membrane structures and maintaining osmotic pressure[2]. Trehalose (hydrate) is widely used in studies of metabolic diseases, neurodegenerative disorders, and food–drug delivery systems[3][4].
In vitro, Trehalose (hydrate) (100mM; 72h) significantly increases the viability of H9c2 cardiomyocytes exposed to high glucose (33mM), decreases the Bax/Bcl-2 ratio and cleaved-caspase-3 protein levels, suppresses NALP3/caspase-1/IL-1β/IL-18-mediated pyroptosis, restores the expression of Beclin-1 and Atg5 proteins as well as the LC3-II/I ratio, and reverses high-glucose–induced autophagic impairment[5].
In vivo, Trehalose (hydrate) (4% w/v in drinking water; 14 days; ad libitum) fully reversed the memory deficit induced by bilateral i.c.v. Aβ25–35 injection, restoring step-through latency in the passive avoidance test to control levels in APP/PS1 mice, while significantly reducing hippocampal CA1 Aβ fluorescence intensity and IBA1-positive microglial density, and restoring neuronal density to control values as shown by Nissl staining[6]. Trehalose (hydrate) (2% w/v in drinking water; ad libitum from 64 days of age until death) significantly delayed disease onset and extended mice lifespan, doubled motor neuron survival in the L4–5 spinal cord, and reduced spinal insoluble SOD1 aggregates in SOD1G93A mice[7].
References:
[1] Megarry AJ, Booth J, Burley J. Amorphous trehalose dihydrate by cryogenic milling. Carbohydr Res. 2011;346(8):1061-1064.
[2] Chen A, Tapia H, Goddard JM, Gibney PA. Trehalose and its applications in the food industry. Compr Rev Food Sci Food Saf. 2022;21(6):5004-5037.
[3] Sharma E, Shruti PS, Singh S, et al. Trehalose and its Diverse Biological Potential. Curr Protein Pept Sci. 2023;24(6):503-517.
[4] Sevriev B, Dimitrova S, Kehayova G, Dragomanova S. Trehalose: Neuroprotective Effects and Mechanisms-An Updated Review. NeuroSci. 2024;5(4):429-444.
[5] Liu Y, Wu S, Zhao Q, et al. Trehalose Ameliorates Diabetic Cardiomyopathy: Role of the PK2/PKR Pathway. Oxid Med Cell Longev. 2021;2021:6779559.
[6] Pupyshev AB, Akopyan AA, Tenditnik MV, et al. Alimentary Treatment with Trehalose in a Pharmacological Model of Alzheimer's Disease in Mice: Effects of Different Dosages and Treatment Regimens. Pharmaceutics. 2024;16(6):813.
[7] Zhang X, Chen S, Song L, et al. MTOR-independent, autophagic enhancer trehalose prolongs motor neuron survival and ameliorates the autophagic flux defect in a mouse model of amyotrophic lateral sclerosis. Autophagy. 2014;10(4):588-602.
















