Targeting AMPK signaling in ischemic/reperfusion injury: From molecular mechanism to pharmacological interventions

Paskeh, Mahshid Deldar Abad; Asadi, Ava; Mirzaei, Sepideh; Hashemi, Mehrdad; Entezari, Maliheh; Raesi, Rasoul; Hushmandi, Kiavash; Zarrabi, Ali; Ertaş, Yavuz Nuri; Aref, Amir Reza; Samarghandian, Saeed; Reíter, Russel J.; Ren, Jun

doi:10.1016/j.cellsig.2022.110323

Cited by 26 publications

(11 citation statements)

References 231 publications

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“…Inflammation is associated with a series of cellular changes, including oxidative stress, ER stress, and changes in cell signaling pathways. These changes can disrupt cellular homeostasis and activate AMPK, which plays a crucial role in regulating the cellular response to inflammation by modulating mitochondrial function, reducing oxidative stress, and inducing autophagy [ 42 ]. By doing so, quercetin and AMPK help to restore cellular homeostasis and prevent cellular damage during inflammation.…”

Section: Natural Products and Neuroprotection And Neuroinflammationmentioning

confidence: 99%

The Potential Benefits of Quercetin for Brain Health: A Review of Anti-Inflammatory and Neuroprotective Mechanisms

Chiang

Tsai

Wang

2023

IJMS

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Neuroinflammation is a critical factor in developing and progressing numerous brain diseases, including neurodegenerative diseases. Chronic or excessive neuroinflammation can lead to neurotoxicity, causing brain damage and contributing to the onset and progression of various brain diseases. Therefore, understanding neuroinflammation mechanisms and developing strategies to control them is crucial for treating brain diseases. Studies have shown that neuroinflammation plays a vital role in the progression of neurodegenerative diseases, such as Alzheimer’s (AD) and Parkinson’s (PD), and stroke. Additionally, the effects of PM2.5 pollution on the brain, including neuroinflammation and neurotoxicity, are well-documented. Quercetin is a flavonoid, a plant pigment in many fruits, vegetables, and grains. Quercetin has been studied for its potential health benefits, including its anti-inflammatory, antioxidant, and anti-cancer properties. Quercetin may also have a positive impact on immune function and allergy symptoms. In addition, quercetin has been shown to have anti-inflammatory and neuroprotective properties and can activate AMP-activated protein kinase (AMPK), a cellular energy sensor that modulates inflammation and oxidative stress. By reducing inflammation and protecting against neuroinflammatory toxicity, quercetin holds promise as a safe and effective adjunctive therapy for treating neurodegenerative diseases and other brain disorders. Understanding and controlling the mechanisms of NF-κB and NLRP3 inflammasome pathways are crucial for preventing and treating conditions, and quercetin may be a promising tool in this effort. This review article aims to discuss the role of neuroinflammation in the development and progression of various brain disorders, including neurodegenerative diseases and stroke, and the impact of PM2.5 pollution on the brain. The paper also highlights quercetin’s potential health benefits and anti-inflammatory and neuroprotective properties.

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Section: Natural Products and Neuroprotection And Neuroinflammationmentioning

confidence: 99%

The Potential Benefits of Quercetin for Brain Health: A Review of Anti-Inflammatory and Neuroprotective Mechanisms

Chiang

Tsai

Wang

2023

IJMS

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“…AMPK is a herotrimeric complex composed of α/β/γ subunits and is activated by activated by upstream kinases (LKB1,CaMKK2, and TAK1) and increased ratio of ADP or AMP/ATP but is inhibited by protein phosphatase 2A and 2C (PP2A, PP2C) and oxidation or acetylation of cysteines in the α subunit [ 39 ]. AMPK is a key energy sensor that modulates cardiac glucose and fatty acid metabolism and exerts beneficial effects against cardiac I/R impairment through multiple mechanisms, which include amelioration of oxidative stress and inflammation, increase in mitochondrial synthesis and improvement of dynamic balance [ 40 ]. Pharmacological activation of AMPK protects against I/R-mediated cardiac myocyte death and contractile dysfunction [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Ursolic Acid Ameliorates Myocardial Ischaemia/Reperfusion Injury by Improving Mitochondrial Function via Immunoproteasome-PP2A-AMPK Signalling

et al. 2023

Nutrients

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Cardiac ischaemia/reperfusion (I/R) injury causes cardiomyocyte apoptosis and mitochondrial dysfunction. Ursolic acid (UA), as a pentacyclic triterpenoid carboxylic acid, exerts several bioactivities in animal models of different diseases, but the preventive role of UA in I/R-induced myocardial dysfunction remains largely unknown. Male wild-type mice were pre-administered with UA at a dosage of 80 mg/kg i.p. and then subjected to cardiac I/R injury for 24 h. Cardiac function and pathological changes were examined by echocardiography and histological staining. The protein and mRNA levels of the genes were determined using qPCR and immunoblotting analysis. Our results revealed that UA administration in mice significantly attenuated the I/R-induced decline in cardiac function, infarct size, myocyte apoptosis, and oxidative stress. Mechanistically, UA increased three immunoproteasome catalytic subunit expressions and activities, which promoted ubiquitinated PP2A degradation and activated AMPK-PGC1α signalling, leading to improved mitochondrial biosynthesis and dynamic balance. In vitro experiments confirmed that UA treatment prevented hypoxia/reperfusion (H/R)-induced cardiomyocyte apoptosis and mitochondrial dysfunction through activation of AMPK signalling. In summary, our findings identify UA as a new activator of the immunoproteasome that exerts a protective role in I/R-induced myocardial dysfunction and suggest that UA supplementation could be beneficial for the prevention of cardiac ischaemic disease.

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“…mTOR inhibits autophagy through two pathways. First, mTOR directly inhibits UNC-51-like kinase 1 (ULK1), which is a key factor in autophagy induction [38]. The second is that mTOR blocks lysosomal biogenesis by inhibiting the nuclear translocation of transcription factor EB (TFEB), thereby indirectly inhibiting autophagy [39][40][41].…”

Section: Structure and Distribution Of Orexin And Its Receptorsmentioning

confidence: 99%

the inhibitory effect of Orexin system on different diseases through mTOR signaling pathway

song

wang

et al. 2022

Preprint

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Orexins, also known as hypocretins, are two neuropeptides secreted from orexin-containing neurons, mainly in the lateral hypothalamus (LH). The mTOR pathway is an essential component of the Orexin/GPCR downstream signaling network and can be activated and activated by Orexin. This review article summarizes the Orexin system and its inhibition of various diseases through mTOR signaling pathway. In addition, the potential of targeting the Orexin system for treating a wide range of conditions is discussed.

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Targeting AMPK signaling in ischemic/reperfusion injury: From molecular mechanism to pharmacological interventions

Cited by 26 publications

References 231 publications

The Potential Benefits of Quercetin for Brain Health: A Review of Anti-Inflammatory and Neuroprotective Mechanisms

The Potential Benefits of Quercetin for Brain Health: A Review of Anti-Inflammatory and Neuroprotective Mechanisms

Ursolic Acid Ameliorates Myocardial Ischaemia/Reperfusion Injury by Improving Mitochondrial Function via Immunoproteasome-PP2A-AMPK Signalling

the inhibitory effect of Orexin system on different diseases through mTOR signaling pathway

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