AMPK and NRF2: Interactive players in the same team for cellular homeostasis?

Petsouki, Eleni; Cabrera, Shara Natalia Sosa; Heiß, Elke H.

doi:10.1016/j.freeradbiomed.2022.07.014

Cited by 54 publications

(30 citation statements)

References 248 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activation of AMPK, SIRT1, and Nrf2 can help preserve bone mass and prevent osteoporosis [171]. Activation of Sestrins and AMPK together with inhibition of mTOR1 can prevent metabolic disorders, neurodegenerative diseases, CVD, cancer, as well as musculoskeletal diseases [172]. Therefore, one key approach in preventing or attenuating AADs is to find means or agents that can activate AMPK-SIRT1-Sestrin signalings, with strong upregulations of Nrf2-HO-1 and AP.…”

Section: Prevention and Attenuation Of Aadsmentioning

confidence: 99%

“…The other approach that can alleviate and prevent AADs is the intake of natural products as nutraceuticals, notably, polyphenols [e.g., berberine, quercetin, myricetin, caffeic acid (CA), and CA ethanolamide (CAEA), CA phenyl ester (CAPE), epigallocatechin-3-gallate (EGCG), gallic acid (GA), curcumin], flavonoids (e.g., resveratol), terpenoids (e.g., ginsenoside and triterpene glycosides), carotenoids, xanthophyll (e.g., astaxanthin), spermidine, and sulforaphane, all of which could act as CR mimetics. Most of these natural compounds have high antioxidation properties, and they can also directly stimulate AMPK (e.g., curcumin, EGCG, spermidine, GA, and CAPE) or SIRT1 (e.g., berberine, EGCG, quercetin, and myricertin) or both (e.g., resveratol, CA, and CAEA), and consequently causing the upregulations of Nrf2 and AP (also see Figure 1) [29,32,171,172,[192][193][194][195]. Some natural compounds can also suppress inflammation (e.g., curcumin, EGCG, and spermidine) [192].…”

Section: Prevention and Attenuation Of Aadsmentioning

confidence: 99%

See 1 more Smart Citation

Oxidative stress, inflammation, dysfunctional redox homeostasis and autophagy cause age-associated diseases

Sobhon

Savedvanich²,

Weerakiet

2023

Exploration of Medicine

View full text Add to dashboard Cite

Aging and age-associated diseases (AADs) are growing risk factors in societies worldwide. During aging, there is an accumulation of excessive oxygen free radicals [reactive oxygen species (ROS)] and nitrogen free radicals [reactive nitrogen species (RNS)] due to dysfunctional mitochondria, dysregulated catalytic activities of cytochrome P450 (CYP), nicotinamide adenine dinucleotide (NAD) phosphate [NADP(H)] oxidase (NOX), cyclooxygenases, and nitric oxide synthases (NOS) over the threshold of physiological levels, creating oxidative stress (OS). Excessive ROS and RNS oxidize, break, denature, and sometimes cause aggregations of key cellular components including DNA, proteins, and lipids. Normally, these denatured molecules and their aggregates are eliminated by autophagy (AP) and ubiquitin-proteosome system (UPS). However, these two proteostatic mechanisms are impaired as age progresses. As a result, these abnormal molecules turn into damage-associated molecular patterns (DAMPs), recognized as non-self by immune cells, leading to systemic chronic inflammation (SCI), which together with OS are the major causes of aging and AADs. Therefore, instead of trying to prevent and cure AADs individually, the logical approach should be the restoration of redox homeostasis by the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway which can prevent the damaging effect of OS and the upregulation of AP and UPS to eliminate DAMPs, and together they attenuate SCI to lessen the effect of inflammation. The central regulators, adenosine monophosphate-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and Sestrins, synergistically control the restoration of the redox homeostasis by activating Nrf2, the upregulation of AP-UPS, and the inhibition of SCI. The activation of these central regulators can be achieved by exercise, caloric restriction (CR), and intakes of certain CR mimetic natural compounds. Consequently, the activations of these regulators may lead to the prevention and/or attenuation of the AADs.

show abstract

Section: Prevention and Attenuation Of Aadsmentioning

confidence: 99%

Section: Prevention and Attenuation Of Aadsmentioning

confidence: 99%

Oxidative stress, inflammation, dysfunctional redox homeostasis and autophagy cause age-associated diseases

Sobhon

Savedvanich²,

Weerakiet

2023

Exploration of Medicine

View full text Add to dashboard Cite

show abstract

“…as well as prevent AADs [190,191]. AMPK and SIRT1 exert their effects through activations of AP and Nrf2 [185,187,189].…”

Section: Extension Of Longevity and Attenuation Of Aadsmentioning

confidence: 99%

“…Co-activation of AMPK and Sestrins could extend longevity and prevent metabolic diseases, including obesity, NAFLD, and diabetes [194]. Activation of AMPK and Sestrins together with the inhibition of mTOR1 can prevent neurodegenerative diseases, CVDs, cancer, as well as musculoskeletal diseases [191]. Therefore, one key approach in extending longevity and preventing or attenuating AADs is to find means or agents that can activate AMPK-SIRT1-Sestrin signaling, which leads to strong upregulations of Nrf2-HO-1 and AP.…”

Section: Extension Of Longevity and Attenuation Of Aadsmentioning

confidence: 99%

Oxidative stress and inflammation: the root causes of aging

Sobhon

Gavin²,

Weerakiet

2023

Exploration of Medicine

View full text Add to dashboard Cite

Oxygen free radicals [reactive oxygen species (ROS)] and nitrogen free radicals [reactive nitrogen species (RNS)] are generated by mitochondria during adenosine triphosphate synthesis, and catalytic activities of cytochrome P450, nicotinamide adenine dinucleotide phosphate oxidases (NOXs), cyclooxygenases, and nitric oxide synthases during drug catabolism, phagocytosis, and acute inflammation. Under normal circumstances, low levels of ROS and RNS provide redox signalings that control many essential physiological processes. As age progresses ROS and RNS increase excessively due to dysfunctional mitochondria, dysregulated NOX, and other free-radical generating sources, leading to oxidative stress, which causes oxidation and denaturation of key cellular components including DNA, proteins, and lipids, which become abnormal, constituting damage-associated molecular pattern (DAMP), recognized as ‘non-self’ by immune cells, leading to inflammation which is mediated by nuclear factor kappa B-inflammasome, p38-c-Jun N-terminal kinase and Janus kinase-signal transducer and activator of transcription pathways. DAMPs are continuously released from damaged and senescent cells, causing an otherwise normally transient inflammation turning into systemic chronic inflammation, the root cause of aging and age-associated diseases (AADs). Cells restore redox balance by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway that induces the synthesis and release of antioxidation molecules and enzymes including haem oxygenase-1, which also inhibits the three inflammatory pathways. Furthermore, upregulation of autophagy (AP) can get rid of abnormal molecules, prevent the generation of DAMPs, and attenuate inflammation. Both AP and Nrf2 signalings decrease with age. The upregulations of Nrf2, AP, and downregulation of inflammation are controlled by sensors of energy and stress levels, i.e., adenosine monophosphate-activated protein kinase, silent information regulator 1, and Sestrins, as well as the extracellular matrix, while mammalian targets for rapamycin complex 1, a nutrient sensor, act in the opposite direction. If the balance of these sensor systems becomes dysregulated, aging process accelerates, and the risk of AADs increases.

show abstract

“…[8], with a focus on energy production, reactive oxygen species generation, calcium signaling, and cell death. Moreover, in the context of energy metabolism, a very exciting link between NRF2 and AMP-activated kinase (AMPK) is described by Petsouki et al [9]. Regarding regulation of NRF2 by kinase cascades, another experimental paper is provided by Ishii et al [10], which proposes that Cav1 serves as a hub for the control of H 2 O 2 -mediated phosphorylation of NRF2 by p38/nSMase2/ceramide signaling.…”

mentioning

confidence: 99%