Status of Research on Sestrin2 and Prospects for its Application in Therapeutic Strategies Targeting Myocardial Aging

Dai, Guolin; Li, Meina; He, Xu; Quan, Nanhu

doi:10.1016/j.cpcardiol.2023.101910

Cited by 3 publications

(1 citation statement)

References 247 publications

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“…A recent study unveiled many transcription factors regulating age-dependent autophagy of the heart such as FoxO, TFEB, hypoxia inducible factor-1 (HIF-1), p53, E2F transcription factor 1 (E2F1), nuclear factor-κB (NF-κB), Kruppel-like factor 4 (KLF4), and zinc finger with KRAB and SCAN domains 3 (ZKSCAN3) ( Shirakabe et al, 2016 ). Many cellular autophagy inhibitors found to be active in aging cells have also been described, including mTOR ( Sciarretta et al, 2012 ; Popov et al, 2023 ) and Mst1 ( Hariharan et al, 2010 ) or inhibition of main autophagy activators, including sestrin2 (Quanet al, 2017; Zahid et al, 2023 ; Dai et al, 2023 ), and sirtuin1 (SIRT1) ( Hariharan et al, 2010 ; Morselli et al, 2010 ). However, the exact mechanism through which cells regulate autophagy and how cells determine the ageing threshold at which an inhibition of autophagy is preferred over activation requires further investigation.…”

Section: Both Autophagy Activation and Inhibition Are Key Factors In ...mentioning

confidence: 99%

The role of autophagy in the progression of HIV infected cardiomyopathy

Sun,

Xu,

Duan

et al. 2024

Front. Cell Dev. Biol.

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Although highly active antiretroviral therapy (HAART) has changed infection with human immunodeficiency virus (HIV) from a diagnosis with imminent mortality to a chronic illness, HIV positive patients who do not develop acquired immunodeficiency syndrome (AIDs) still suffer from a high rate of cardiac dysfunction and fibrosis. Regardless of viral load and CD count, HIV-associated cardiomyopathy (HIVAC) still causes a high rate of mortality and morbidity amongst HIV patients. While this is a well characterized clinical phenomena, the molecular mechanism of HIVAC is not well understood. In this review, we consolidate, analyze, and discuss current research on the intersection between autophagy and HIVAC. Multiple studies have linked dysregulation in various regulators and functional components of autophagy to HIV infection regardless of mode of viral entry, i.e., coronary, cardiac chamber, or pericardial space. HIV proteins, including negative regulatory factor (Nef), glycoprotein 120 (gp120), and transactivator (Tat), have been shown to interact with type II microtubule-associated protein-1 β light chain (LC3-II), Rubiquitin, SQSTM1/p62, Rab7, autophagy-specific gene 7 (ATG7), and lysosomal-associated membrane protein 1 (LAMP1), all molecules critical to normal autophagy. HIV infection can also induce dysregulation of mitochondrial bioenergetics by altering production and equilibrium of adenosine triphosphate (ATP), mitochondrial reactive oxygen species (ROS), and calcium. These changes alter mitochondrial mass and morphology, which normally trigger autophagy to clear away dysfunctional organelles. However, with HIV infection also triggering autophagy dysfunction, these abnormal mitochondria accumulate and contribute to myocardial dysfunction. Likewise, use of HAART, azidothymidine and Abacavir, have been shown to induce cardiac dysfunction and fibrosis by inducing abnormal autophagy during antiretroviral therapy. Conversely, studies have shown that increasing autophagy can reduce the accumulation of dysfunctional mitochondria and restore cardiomyocyte function. Interestingly, Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, has also been shown to reduce HIV-induced cytotoxicity by regulating autophagy-related proteins, making it a non-antiviral agent with the potential to treat HIVAC. In this review, we synthesize these findings to provide a better understanding of the role autophagy plays in HIVAC and discuss the potential pharmacologic targets unveiled by this research.

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Section: Both Autophagy Activation and Inhibition Are Key Factors In ...mentioning

confidence: 99%

The role of autophagy in the progression of HIV infected cardiomyopathy

Sun,

Xu,

Duan

et al. 2024

Front. Cell Dev. Biol.

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Allicin regulates Sestrin2 ubiquitination to affect macrophage autophagy and senescence, thus inhibiting the growth of hepatoma cells

Kong,

Li,

Pan

et al. 2024

Tissue and Cell

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Anti-Aging Effects of Flavonoids from Plant Extracts

Păcularu-Burada,

Cîrîc,

Begea

2024

Foods

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Aging is a natural and irreversible process, affecting living organisms by negatively impacting the tissues’ and cells’ morphology and functionality and consequently being responsible for aging-related diseases. Taking into account the actual preoccupations of both consumers and researchers, healthy anti-aging alternatives are being intensively studied in order to address such concerns. Due to their functional features, plant flavonoids can be considered valuable nutraceuticals. This paper highlights the possibilities to use flavonoids extracted from various plants for their anti-aging potential on the skin, brain, and heart. Moreover, their anticarcinogenic, anti-inflammatory, and anti-diabetic properties are summarized, along with the senescence-associated mechanisms. Both the nutraceutical and cosmeceutical fields are continuously developing and flavonoids originating from plants are promising candidates to obtain such products. Thus, the bioactive compounds’ extraction and their subsequent involvement in innovative product manufacturing must be carefully performed while being aware of the various intrinsic and extrinsic factors that may affect the phytochemicals’ structures, bioavailability, and health effects.

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Status of Research on Sestrin2 and Prospects for its Application in Therapeutic Strategies Targeting Myocardial Aging

Cited by 3 publications

References 247 publications

The role of autophagy in the progression of HIV infected cardiomyopathy

The role of autophagy in the progression of HIV infected cardiomyopathy

Allicin regulates Sestrin2 ubiquitination to affect macrophage autophagy and senescence, thus inhibiting the growth of hepatoma cells

Anti-Aging Effects of Flavonoids from Plant Extracts

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