Potential Roles of Sestrin2 in Alzheimer’s Disease: Antioxidation, Autophagy Promotion, and Beyond

Chen, Shang-Der; Yang, Jen Ming; Hsieh, Yi-Heng; Lin, Tsu-Kung; Lin, Yi‐Chun; Chao, A-Ching; Yang, Ding-I

doi:10.3390/biomedicines9101308

Cited by 5 publications

(3 citation statements)

References 148 publications

(227 reference statements)

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“…The exploration of Therapeutic strategies through mediation of Sestrin2 is now underway. Several natural products and medications in diabetes have been shown to alter the expression levels of Sestrin2, which lead to the possibility of novel treatments in diabetes and diabetic complications targeting Sestrin2 and the associated pathways ( 211 ). Initially, a few studies investigated the potential mediator of Sestrin2 in the field of tumor therapies, including several small molecules ( 212 ).…”

Section: Possible Pharmacological Mediators Of Sestrin2mentioning

confidence: 99%

Sestrin2 in diabetes and diabetic complications

Zhang,

Luo,

et al. 2023

Front. Endocrinol.

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Diabetes is a global health problem which is accompanied with multi-systemic complications. It is of great significance to elucidate the pathogenesis and to identify novel therapies of diabetes and diabetic complications. Sestrin2, a stress-inducible protein, is primarily involved in cellular responses to various stresses. It plays critical roles in regulating a series of cellular events, such as oxidative stress, mitochondrial function and endoplasmic reticulum stress. Researches investigating the correlations between Sestrin2, diabetes and diabetic complications are increasing in recent years. This review incorporates recent findings, demonstrates the diverse functions and regulating mechanisms of Sestrin2, and discusses the potential roles of Sestrin2 in the pathogenesis of diabetes and diabetic complications, hoping to highlight a promising therapeutic direction.

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Section: Possible Pharmacological Mediators Of Sestrin2mentioning

confidence: 99%

Sestrin2 in diabetes and diabetic complications

Zhang,

Luo,

et al. 2023

Front. Endocrinol.

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“…Sestrin-2, a pressure sensor protein, was found to have a neuroprotective effect by polarizing microglia cells in the ischemic mouse brain from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype ( 32 ). By augmenting sestrin-2 expression in disease models, the function of neurons was enhanced, allowing them to cope with oxidative stress and thus adapt to stressful conditions ( 33 ). A previous study has shown that patients with primary insomnia had a reduced ability to resist oxidative stress ( 34 ).…”

Section: Introductionmentioning

confidence: 99%

Serum levels of neurotensin, pannexin-1, and sestrin-2 and the correlations with sleep quality or/and cognitive function in the patients with chronic insomnia disorder

Su,

Ma,

et al. 2024

Front. Psychiatry

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ObjectivesTo examine serum concentrations of neurotensin, pannexin-1 and sestrin-2, and their correlations with subjective and objective sleep quality and cognitive function in the patients with chronic insomnia disorder (CID).MethodsSixty-five CID patients were enrolled continuously and fifty-six good sleepers in the same period were served as healthy controls (HCs). Serum levels of neurotensin, pannexin-1 and sestrin-2 were measured by enzyme-linked immunosorbent assays. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and polysomnography, and mood was evaluated by 17-item Hamilton Depression Rating Scale. General cognitive function was assessed with the Chinese-Beijing Version of Montreal Cognitive Assessment and spatial memory was evaluated by Blue Velvet Arena Test (BVAT).ResultsRelative to the HCs, the CID sufferers had higher levels of neurotensin (t=5.210, p<0.001) and pannexin-1 (Z=−4.169, p<0.001), and lower level of sestrin-2 (Z=−2.438, p=0.015). In terms of objective sleep measures, pannexin-1 was positively associated with total sleep time (r=0.562, p=0.002) and sleep efficiency (r=0.588, p=0.001), and negatively with wake time after sleep onset (r=−0.590, p=0.001) and wake time (r=−0.590, p=0.001); sestrin-2 was positively associated with percentage of rapid eye movement sleep (r=0.442, p=0.016) and negatively with non-rapid eye movement sleep stage 2 in the percentage (r=−0.394, p=0.034). Adjusted for sex, age and HAMD, pannexin-1 was still associated with the above objective sleep measures, but sestrin-2 was only negatively with wake time (r=−0.446, p=0.022). However, these biomarkers showed no significant correlations with subjective sleep quality (PSQI score). Serum concentrations of neurotensin and pannexin-1 were positively associated with the mean erroneous distance in the BVAT. Adjusted for sex, age and depression, neurotensin was negatively associated with MoCA score (r=−0.257, p=0.044), pannexin-1 was positively associated with the mean erroneous distance in the BVAT (r=0.270, p=0.033).ConclusionsThe CID patients had increased neurotensin and pannexin-1 and decreased sestrin-2 in the serum levels, indicating neuron dysfunction, which could be related to poor sleep quality and cognitive dysfunction measured objectively.

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“…Some molecules, such as amarogentin, seem able to interact with this receptor, representing potential candidates for future clinical studies [4]. Other classes of newer drugs, such as SGLT-2 inhibitors [5] and sestrins [6], could be considered to reduce mTOR activity, acting after the insulin receptor cascade and slowing neurodegeneration. Sestrins seem able to also act in other commonly disrupted pathways in AD, such as, for example, by improving antioxidation and adjusting autophagy.…”

mentioning

confidence: 99%