Fingolimod Alleviates Cognitive Deficit in Type 2 Diabetes by Promoting Microglial M2 Polarization via the pSTAT3-jmjd3 Axis

Sood, Anika; Fernandes, Valencia; Kumari, Preeti; Khot, Mayuri; Khatri, Dharmendra Kumar; Singh, Shashi Bala

doi:10.1007/s12035-022-03120-x

Cited by 13 publications

(6 citation statements)

References 56 publications

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“…According to recent studies, one of the most promising treatment options for diabetes may be to boost the polarization of the macrophage M2 phenotype to reduce insulin resistance and stabilize glucose/lipid metabolism ( 85 – 87 ). Additionally, this therapy may assist patients with diabetes in diminishing endothelial dysfunction and preventing complications of diabetes ( 88 – 90 ).…”

Section: Macrophage/microglia Polarization In Drmentioning

confidence: 99%

Macrophage/microglia polarization for the treatment of diabetic retinopathy

Yao,

Li,

Zhou

et al. 2023

Front. Endocrinol.

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Macrophages/microglia are immune system defense and homeostatic cells that develop from bone marrow progenitor cells. According to the different phenotypes and immune responses of macrophages (Th1 and Th2), the two primary categories of polarized macrophages/microglia are those conventionally activated (M1) and alternatively activated (M2). Macrophage/microglial polarization is a key regulating factor in the development of inflammatory disorders, cancers, metabolic disturbances, and neural degeneration. Macrophage/microglial polarization is involved in inflammation, oxidative stress, pathological angiogenesis, and tissue healing processes in ocular diseases, particularly in diabetic retinopathy (DR). The functional phenotypes of macrophages/microglia affect disease progression and prognosis, and thus regulate the polarization or functional phenotype of microglia at different DR stages, which may offer new concepts for individualized therapy of DR. This review summarizes the involvement of macrophage/microglia polarization in physiological situations and in the pathological process of DR, and discusses the promising role of polarization in personalized treatment of DR.

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Section: Macrophage/microglia Polarization In Drmentioning

confidence: 99%

Macrophage/microglia polarization for the treatment of diabetic retinopathy

Yao,

Li,

Zhou

et al. 2023

Front. Endocrinol.

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“…However, many studies have found that animal models with DM treated with FTY720 have significant improvements in its complications, but it has no significant effect on lowering blood glucose. 12 , 14 , 35 , 36 This may be due to these differences in the model building, the dosage and method of medication. Hence, in the future, the role of FTY720 in diabetes control needs to be further evaluated in large-scale and long-term studies.…”

Section: Introductionmentioning

confidence: 99%

“… 71 A recent study has confirmed that FTY720 induces the polarization of M1 to M2 through the pstat3-jmjd3 axis to improve neuroinflammatory response, further inhibit neuronal apoptosis, improve synaptic plasticity, and provide neuroprotection for diabetic mice. 14 In addition, by inhibiting S1PL in the prefrontal cortex and hippocampus of T2DM mice, FTY720 further reduces P53 level and promotes TP53-associated glycolysis and apoptosis regulator expression, thereby increasing anti-inflammatory microglial phenotype and inhibiting apoptosis in the brain of diabetic mice. 72 …”

Section: Introductionmentioning

confidence: 99%

“…9 More and more evidence shows that FTY720 has an anti-diabetic effect and a good therapeutic effect in DM complications, so it is expected to become a new strategy for the treatment of DM and its chronic complications. 8,[12][13][14] In this article, we summarize the application of FTY720 in the treatment of DM and its related chronic complications. In addition, the review elucidates potential mechanisms and discusses the challenges associated with its application.…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic Potential of Fingolimod in Diabetes Mellitus and Its Chronic Complications

Li,

Nan,

et al. 2024

DMSO

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Diabetes mellitus is a metabolic disease characterized by elevated blood glucose due to a deficiency of insulin secretion and/or action. Long-term poor blood glucose control may lead to chronic damage and dysfunction of the heart, kidneys, eyes, and other organs. Therefore, it is important to develop treatments for diabetes and its chronic complications. Fingolimod is a structural sphingosine analogue and sphingosine-1-phosphate receptor modulator currently used for the treatment of relapsing-remitting multiple sclerosis. Several studies have shown that it has beneficial effects on the improvement of diabetes and its chronic complications. This paper reviews the therapeutic potential of Fingolimod in diabetes and its chronic complications, aiming to further guide future treatment strategies.

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“…Microglia, immune cells within the central nervous system, play a pivotal role in initiating and perpetuating in ammatory responses in the brain [23,24]. Additionally, M2 polarization of microglia may contribute to cognitive impairment in individuals with T2DM [25].…”

Section: Introductionmentioning

confidence: 99%

The short-chain fatty acid propionate exacerbates anxiety and cognitive deficits in high-fat diet-induced obese mice by impairing hippocampal neurogenesis and neuroinflammation

Zuo,

Bai,

Zhao

et al. 2024

Preprint

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Short-chain fatty acid propionate is a frequently used food preservative. However, excessive use of preservatives can pose environmental and public health risks. In addition, type 2 diabetes mellitus (T2DM) is a significant global public health concern. This study investigates whether propionate exposure affects the molecular mechanisms underlying the development of insulin resistance and neurobehavioral effects in high-fat diet mice. In this study, six-week-old male Balb/c mice were divided into four groups: standard diet (SD), propionate (15 mg/kg) (Pro), high-fat diet (HFD), and HFD supplemented with propionate (15 mg/kg) (HFD + Pro). After six weeks, the results indicated that exposure to HFD + Pro led to exacerbated weight gain, and fatty liver pathological changes, and affected glucose metabolism and insulin resistance compared to HFD mice. Furthermore, the HFD + Pro mice displayed heightened anxiety and depression behaviors in the elevated plus maze and forced swim tests, as well as cognitive and social impairments in the novel object recognition and social interaction tests. Additionally, HFD + Pro affects neuronal morphology and results in hippocampal loss, activates microglia, and leads to upregulation of neuroinflammatory factors IL-6 and IL-1β, and downregulation of IL-4 and IL-10. In conclusion, propionate exacerbates insulin resistance, impairs hippocampal neurogenesis and produces neuroinflammation, leading to behavioral deficits in HFD mice, this study provides evidence supporting the involvement of propionate in the pathogenesis of T2DM and brain neurobehavioral abnormalities. Further assessment of propionate safety is warranted.

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Fingolimod Alleviates Cognitive Deficit in Type 2 Diabetes by Promoting Microglial M2 Polarization via the pSTAT3-jmjd3 Axis

Cited by 13 publications

References 56 publications

Macrophage/microglia polarization for the treatment of diabetic retinopathy

Macrophage/microglia polarization for the treatment of diabetic retinopathy

Therapeutic Potential of Fingolimod in Diabetes Mellitus and Its Chronic Complications

The short-chain fatty acid propionate exacerbates anxiety and cognitive deficits in high-fat diet-induced obese mice by impairing hippocampal neurogenesis and neuroinflammation

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