Novel Role of the SIRT1 in Endocrine and Metabolic Diseases

Lu, Chenxi; Zhao, Huadong; Liu, Yanqing; Liu, Yang; Yao, Hairong; Liu, Tong; Gou, Tiantian; Wang, Li; Zhang, Juan; Tian, Ye; Yang, Yang; Zhang, Huan

doi:10.7150/ijbs.78654

Cited by 51 publications

(13 citation statements)

References 238 publications

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“…Modulating SIRT1 activity counteracts the aging process, inducing neuronal vitality, adjusting cellular homeostatic defense against stress, and superimposing a paramount life longevity impact (Mishra et al 2021 ; Ziętara et al 2022 ). SIRT1 overexpression also fosters insulin signaling by impairing PTP1B, a major inhibitor of insulin receptor (Sun et al 2007 ; Lu et al 2023a ; Wu et al 2023 ). In response to PTP1B inhibition, IGF1 binds to its corresponding receptor and triggers downstream neuroprotective signaling pathways of PI3K/AKT (Yang et al 2018 ; Li et al 2023a ; Tuohongerbieke et al 2023 ).…”

Section: Discussionmentioning

confidence: 99%

PI3K/AKT signaling activation by roflumilast ameliorates rotenone-induced Parkinson’s disease in rats

et al. 2023

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Parkinson’s disease (PD) is the second most common progressive age-related neurodegenerative disorder. Paramount evidence shed light on the role of PI3K/AKT signaling activation in the treatment of neurodegenerative disorders. PI3K/AKT signaling can be activated via cAMP-dependent pathways achieved by phosphodiesterase 4 (PDE4) inhibition. Roflumilast is a well-known PDE4 inhibitor that is currently used in the treatment of chronic obstructive pulmonary disease. Furthermore, roflumilast has been proposed as a favorable candidate for the treatment of neurological disorders. The current study aimed to unravel the neuroprotective role of roflumilast in the rotenone model of PD in rats. Ninety male rats were allocated into six groups as follows: control, rotenone (1.5 mg/kg/48 h, s.c.), L-dopa (22.5 mg/kg, p.o), and roflumilast (0.2, 0.4 or 0.8 mg/kg, p.o). All treatments were administrated for 21 days 1 h after rotenone injection. Rats treated with roflumilast showed an improvement in motor activity and coordination as well as preservation of dopaminergic neurons in the striatum. Moreover, roflumilast increased cAMP level and activated the PI3K/AKT axis via stimulation of CREB/BDNF/TrkB and SIRT1/PTP1B/IGF1 signaling cascades. Roflumilast also caused an upsurge in mTOR and Nrf2, halted GSK-3β and NF-ĸB, and suppressed FoxO1 and caspase-3. Our study revealed that roflumilast exerted neuroprotective effects in rotenone-induced neurotoxicity in rats. These neuroprotective effects were mediated via the crosstalk between CREB/BDNF/TrkB and SIRT1/PTP1B/IGF1 signaling pathways which activates PI3K/AKT trajectory. Therefore, PDE4 inhibition is likely to offer a reliable persuasive avenue in curing PD via PI3K/AKT signaling activation. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

PI3K/AKT signaling activation by roflumilast ameliorates rotenone-induced Parkinson’s disease in rats

et al. 2023

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“…Among the sirtuins, SIRT1 is the most extensively studied member. It is associated with insulin sensitivity, tumorigenesis, and the regulation of essential metabolic pathways [ 125 ].…”

Section: Relationship Of Antioxidant Metabolism Pathways Sirtuins And...mentioning

confidence: 99%

Antioxidant Metabolism Pathways in Vitamins, Polyphenols, and Selenium: Parallels and Divergences

Andrés,

Pérez de la Lastra,

Juan

et al. 2024

IJMS

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Free radicals (FRs) are unstable molecules that cause reactive stress (RS), an imbalance between reactive oxygen and nitrogen species in the body and its ability to neutralize them. These species are generated by both internal and external factors and can damage cellular lipids, proteins, and DNA. Antioxidants prevent or slow down the oxidation process by interrupting the transfer of electrons between substances and reactive agents. This is particularly important at the cellular level because oxidation reactions lead to the formation of FR and contribute to various diseases. As we age, RS accumulates and leads to organ dysfunction and age-related disorders. Polyphenols; vitamins A, C, and E; and selenoproteins possess antioxidant properties and may have a role in preventing and treating certain human diseases associated with RS. In this review, we explore the current evidence on the potential benefits of dietary supplementation and investigate the intricate connection between SIRT1, a crucial regulator of aging and longevity; the transcription factor NRF2; and polyphenols, vitamins, and selenium. Finally, we discuss the positive effects of antioxidant molecules, such as reducing RS, and their potential in slowing down several diseases.

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“…SIRT1, a nicotinamide adenine dinucleotide-dependent deacetylase, is a key regulator of energy metabolism that significantly affects metabolism, inflammation, and autophagy regulation ( 72–74 ). It has been demonstrated that metformin can promote chondrocyte autophagy and reduce chondrocyte apoptosis through the AMPKα2/SIRT1 pathway to alleviate osteoarthritis, and the protective effect of metformin is reversed by silencing AMPKα2 or blocking SIRT1 expression ( 57 ).…”

Section: Mechanism Of Action Of Metforminmentioning

confidence: 99%

Mechanisms and effects of metformin on skeletal muscle disorders

Shang,

Miao

2023

Front. Neurol.

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Skeletal muscle disorders are mostly genetic and include several rare diseases. With disease progression, muscle fibrosis and adiposis occur, resulting in limited mobility. The long course of these diseases combined with limited treatment options affect patients both psychologically and economically, hence the development of novel treatments for neuromuscular diseases is crucial to obtain a better quality of life. As a widely used hypoglycemic drug in clinical practice, metformin not only has anti-inflammatory, autophagy-regulating, and mitochondrial biogenesis-regulating effects, but it has also been reported to improve the symptoms of neuromuscular diseases, delay hypokinesia, and regulate skeletal muscle mass. However, metformin’s specific mechanism of action in neuromuscular diseases requires further elucidation. This review summarizes the evidence showing that metformin can regulate inflammation, autophagy, and mitochondrial biogenesis through different pathways, and further explores its mechanism of action in Duchenne muscular dystrophy, statin-associated muscle disorders, and age-related sarcopenia. This review clarifies the directions of future research on therapy for neuromuscular diseases.

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Novel Role of the SIRT1 in Endocrine and Metabolic Diseases

Cited by 51 publications

References 238 publications

PI3K/AKT signaling activation by roflumilast ameliorates rotenone-induced Parkinson’s disease in rats

PI3K/AKT signaling activation by roflumilast ameliorates rotenone-induced Parkinson’s disease in rats

Antioxidant Metabolism Pathways in Vitamins, Polyphenols, and Selenium: Parallels and Divergences

Mechanisms and effects of metformin on skeletal muscle disorders

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