Trehalose-based neuroprotective autophagy inducers

Assoni, Giulia; Frapporti, Giulia; Colombo, Eleonora; Gornati, Davide; Posadas, Inmaculada; Polito, Laura; Seneci, Pierfausto; Piccoli, Giovanni

doi:10.1016/j.bmcl.2021.127929

Cited by 19 publications

(15 citation statements)

References 27 publications

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“…As reported in previous [ 34 , 35 ] and current studies [ 36 , 37 ], trehalose is neuroprotective in various animal models of neurodegenerative diseases.…”

Section: Discussionsupporting

confidence: 73%

Trehalose Suppresses Lysosomal Anomalies in Supporting Cells of Oocytes and Maintains Female Fertility

et al. 2022

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Supporting cells of oocytes, i.e., cumulus cells, control oocyte quality, which determines fertilization success. Therefore, the transformation of mature and immature cumulus cells (MCCs and ICCs, respectively) into dysmature cumulus cells (DCCs) with dead characteristics deteriorates oocyte quality. However, the molecular basis for this transformation remains unclear. Here, we explored the link between autophagic decline and cumulus transformation using cumulus cells from patients with infertility, female mice, and human granulosa cell-derived KGN cell lines. When human cumulus cells were labeled with LysoTracker probes, fluorescence corresponding to lysosomes was enhanced in DCCs compared to that in MCCs and ICCs. Similarly, treatment with the autophagy inhibitor chloroquine elevated LysoTracker fluorescence in both mouse cumulus cells and KGN cells, subsequently suppressing ovulation in female mice. Electron microscopy analysis revealed the proliferation of abnormal lysosomes in chloroquine-treated KGN cells. Conversely, the addition of an autophagy inducer, trehalose, suppressed chloroquine-driven problematic lysosomal anomalies and ameliorated ovulation problems. Our results suggest that autophagy maintains the healthy state of the supporting cells of human oocytes by suppressing the formation of lysosomes. Thus, our results provide insights into the therapeutic effects of trehalose on female fertility.

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“…As reported in previous [ 34 , 35 ] and current studies [ 36 , 37 ], trehalose is neuroprotective in various animal models of neurodegenerative diseases.…”

Section: Discussionsupporting

confidence: 73%

Trehalose Suppresses Lysosomal Anomalies in Supporting Cells of Oocytes and Maintains Female Fertility

et al. 2022

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“…The protective role of trehalose by induction of autophagy has been shown in many studies (8,9,34). In one study Trehalose has neuroprotective effects on the substantia nigra dopaminergic cells by activating autophagy and non-canonical nrf2 pathways (9).…”

Section: U N C O R R E C T E Dmentioning

confidence: 95%

rehalose and carnosic acid induced LC3I, LC3II ratio, P62 down–regulation and cleaved caspase 3 expression in neural stem cells

HAGHDOOST-YAZDI¹,

ABBASZADEH²,

HAMIDABADI³

et al. 2022

BLL

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BACKGROUND: Using neural stem cells ( NSCs) in cell therapy and regenerative medicine is a growing knowledge. In this study, the protective role of carnosic acid and trehalose against H 2 O 2 -induced oxidative stress in autophagy induction and apoptosis inhibition in NSCs was investigated. MATERIAL AND METHODS: The bone marrow stromal cells (BMSCs) were isolated from the femur of the rat and differentiated into NSCs using basic fi broblast and epidermal growth factors (bFGF and EGF), and B27 serum free media. To evaluate the autophagy, the P62 protein was assessed by immunocytochemistry and LC3II / LC3I ratio by Western blotting. Further, we used 3-Methyladenine (3-MA), a widely used autophagy inhibitor to study whether combined treatment of 3-MA with carnosic acid and trehalose modulates autophagy in NSCs. For studying apoptosis, the cleaved caspase-3 protein was evaluated. Carnosic acid and trehalose increased the survival of the NSCs. RESULTS: The H 2 O 2 decreased the autophagy and induced apoptosis with increasing time during 24 hours, however, a pre-treatment with 2 μM carnosic acid and trehalose 3 % induced the autophagy proteins (while increasing the LC3II / LC3I ratio and decreasing the P62) and decreased the apoptosis (while decreasing the expression of the cleaved caspase-3). The results showed that the carnosic acid and trehalose increased the survival of NSCs against the oxidative stress caused by H 2 O 2 , decreased apoptosis, and induced autophagy. CONCLUSION: Due to the carnosic acid and trehalose unique properties and its low toxicity, it can be used as an agent in cellular transplantation for reducing oxidative stress and inducing autophagy (Fig. 4, Ref. 37).

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“…In terms of academic research, trehalose has long been used as a stabilizer for a variety of biologics, such as protein and genetic material, viruses, and microorganisms, 123 or as a cryoprotectant for cells and tissues. 124 Moreover, trehalose is being explored as a therapeutic for cancer 125 and metabolic diseases, 126 as an autophagy inducer, 127 and as a stabilizer for nebulized formulations that does not induce toxicity in the lungs, 128 among many other applications. However, in the past decade, poly(trehalose) has emerged as a promising and potentially superior alternative to the sugar alone.…”

Section: Outlook and Future Perspectivementioning

confidence: 99%

Synthesis and Application of Trehalose Materials

Vinciguerra

Gelb

Maynard

2022

JACS Au

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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.

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Trehalose-based neuroprotective autophagy inducers

Cited by 19 publications

References 27 publications

Trehalose Suppresses Lysosomal Anomalies in Supporting Cells of Oocytes and Maintains Female Fertility

Trehalose Suppresses Lysosomal Anomalies in Supporting Cells of Oocytes and Maintains Female Fertility

rehalose and carnosic acid induced LC3I, LC3II ratio, P62 down–regulation and cleaved caspase 3 expression in neural stem cells

Synthesis and Application of Trehalose Materials

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