Natural Products Targeting ER Stress, and the Functional Link to Mitochondria

Martucciello, Stefania; Masullo, Milena; Cerulli, Antonietta; Piacente, Sonia

doi:10.3390/ijms21061905

Cited by 78 publications

(61 citation statements)

References 61 publications

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“…ER and mitochondria are closely related to each other, and their main tasks are Ca++ homeostasis, autophagy, and apoptosis, in addition to the regulation of innate and adaptive immune responses during viral infections [119] , [123] , [124] , [125] . Studies have identified several SARS-CoV proteins with an ability to manipulate ER and mitochondria proteins, and thus enabling the virus to escape from host cell defense and continue to replicate [119] , [122] .…”

Section: Inhibition Of Endoplasmic Reticulum-mitochondrial Stress As mentioning

confidence: 99%

“…Besides, reduced oxidative phosphorylation would lead to T cell exhaustion [118] . Furthermore, by affecting Ca++ homeostasis, ROS causes Ca++ to leakage from the ER into the mitochondria, which ultimately leads to the destruction of the inner mitochondrial membrane [120] , [123] , [126] . Based on the pathology evidence of COVID-19 patients, viral particles in ER and mitochondria were observed to be dilated and swollen, respectively [120] .…”

Section: Inhibition Of Endoplasmic Reticulum-mitochondrial Stress As mentioning

confidence: 99%

“…It is possible that mtDNA secretion may be involved in the formation of cytokine storms in COVID-19 patients [73] . Meanwhile, ER-mitochondrial stress is associated with diabetes, cancer, viral infections, neurological diseases, and gastrointestinal disorders [120] , [123] , [126] .…”

Section: Inhibition Of Endoplasmic Reticulum-mitochondrial Stress As mentioning

confidence: 99%

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SARS-CoV-2: From the pathogenesis to potential anti-viral treatments

Zarandi¹,

Zinatizadeh²,

Zinatizadeh³

et al. 2021

Biomedicine & Pharmacotherapy

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Introduction The world is witnessing the spread of one of the members of Coronaviruses (CoVs) family, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the 21st century. Considering the short time spent after its prevalence, limited information is known about the effect of the virus mechanism on different organs of the body; meanwhile the lack of specific treatment and vaccine for this virus has exposed millions of people to a big challenge. Areas covered The review article aims to describe the general and particular characteristics of CoVs, their classification, genome structure, host cell infection, cytokine storm, anti-viral treatments, and inhibition of COVID-19-related ER-mitochondrial stress. In addition, it refers to drugs such as Chloroquine/Hydroxychloroquine, Lopinavir/Ritonavir, darunavir, ribavirin, remdesivir, and favipiravir, which have undergone clinical trials for coronavirus disease 2019 (COVID-19) treatment. This analysis was derived from an extensive scientific literature search including Pubmed, ScienceDirect, and Google Scholar performed. Expert opinion The effectiveness rate and complications of these drugs can reveal new insights into the potential therapeutic goals for the disease. Moreover, lifestyle change can effectively prevent SARS-CoV-2 infection.

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Section: Inhibition Of Endoplasmic Reticulum-mitochondrial Stress As mentioning

confidence: 99%

Section: Inhibition Of Endoplasmic Reticulum-mitochondrial Stress As mentioning

confidence: 99%

See 1 more Smart Citation

SARS-CoV-2: From the pathogenesis to potential anti-viral treatments

Zarandi¹,

Zinatizadeh²,

Zinatizadeh³

et al. 2021

Biomedicine & Pharmacotherapy

View full text Add to dashboard Cite

show abstract

“…In particular, it has been found that ER and oxidative stress lead to impairment of the so-called unfolded protein response (UPR), which is a compensatory mechanism that contributes to maintenance of the myocardial cell integrity. This involves complex molecular pathways, probably driven by eukaryotic translation initiation factor 2 alpha (eIF2α) phosphorylation and protein kinase RNA-like ER Kinase (PERK) and leading to a compensatory response to ER stress, although this needs to be better clarified [ 130 , 131 , 132 , 133 , 134 , 135 , 136 ]. Furthermore, an increase in intracellular Glucose-Regulated Protein 78 (GRP78), considered to be a chaperone of ER stress and, most importantly, a regulator of UPR, has been shown to play a role in these mechanisms [ 132 , 133 , 134 , 135 , 136 ].…”

Section: Emerging Pathophysiological Mechanisms Involved In the Onmentioning

confidence: 99%

Pathophysiological Basis for Nutraceutical Supplementation in Heart Failure: A Comprehensive Review

et al. 2021

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There is evidence demonstrating that heart failure (HF) occurs in 1–2% of the global population and is often accompanied by comorbidities which contribute to increasing the prevalence of the disease, the rate of hospitalization and the mortality. Although recent advances in both pharmacological and non-pharmacological approaches have led to a significant improvement in clinical outcomes in patients affected by HF, residual unmet needs remain, mostly related to the occurrence of poorly defined strategies in the early stages of myocardial dysfunction. Nutritional support in patients developing HF and nutraceutical supplementation have recently been shown to possibly contribute to protection of the failing myocardium, although their place in the treatment of HF requires further assessment, in order to find better therapeutic solutions. In this context, the Optimal Nutraceutical Supplementation in Heart Failure (ONUS-HF) working group aimed to assess the optimal nutraceutical approach to HF in the early phases of the disease, in order to counteract selected pathways that are imbalanced in the failing myocardium. In particular, we reviewed several of the most relevant pathophysiological and molecular changes occurring during the early stages of myocardial dysfunction. These include mitochondrial and sarcoplasmic reticulum stress, insufficient nitric oxide (NO) release, impaired cardiac stem cell mobilization and an imbalanced regulation of metalloproteinases. Moreover, we reviewed the potential of the nutraceutical supplementation of several natural products, such as coenzyme Q10 (CoQ10), a grape seed extract, Olea Europea L.-related antioxidants, a sodium–glucose cotransporter (SGLT2) inhibitor-rich apple extract and a bergamot polyphenolic fraction, in addition to their support in cardiomyocyte protection, in HF. Such an approach should contribute to optimising the use of nutraceuticals in HF, and the effect needs to be confirmed by means of more targeted clinical trials exploring the efficacy and safety of these compounds.

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“…In particular, activated during stress conditions, protein kinase RNA-like ER kinase (PERK) is a mediator of eIF2α phosphorylation following folded protein exposure, thus preventing protein synthesis by selectively prompting Activating Transcription Factor 4 (ATF4) translation in the instantaneous response to ER stress [141,142]. Importantly, ER stress markers are involved in the PERK/eIF2α signalling pathway, which also promotes ER stress and contributes to organ injury induced through ER stress-mediated apoptosis [145,146,147]. Increased intracellular GRP78, considered to be a marker of unfolded protein response (UPR) and chaperone of ER stress, demonstrates unfolded and mis-folded protein aggregation in ER and UPR [148,149].…”

Section: Sarcoplasmic Reticulum Stress In Hfmentioning

confidence: 99%

Pathophysiological Basis for Nutraceutical Supplementation in Heart Failure: A Comprehensive Review

Mollace¹,

Rosano²,

Anker³

et al. 2020

Preprint

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Heart failure (HF) is a disease state which has been shown to affect 1-2% of the global population, being often associated with comorbidities such as diabetes, hypertension, obesity or hyperlipidaemia which increase the prevalence of the disease, the rate of hospitalization and the mortality. Although recent advances in both pharmacological and non pharmacological approaches have led to significant improvements in clinical outcomes in patients affected by HF, residual unmet needs remain. Treatment of the disease remains unclear particularly related to poorly defined strategies in the early stages of myocardial dysfunction. Nutritional support in patients developing HF and nutraceutical supplementation have recently been shown to may contribute in the protection of the failing myocardium, though their place in the treatment of HF still needs to be better clarified. In this context, the ONUS-HF working group aimed to assess the optimal nutraceutical approach to HF in the early phases of the disease in order to counteract selected pathways which are imbalanced in the failing myocardium. In particular, we reviewed several of the most relevant pathophysiological and molecular changes occurring druing the early stages of myocardial dysfunction. These include mitochondrial and sarcoplasmic reticulum stress, insufficient nitric oxide (NO) release, cardiac stem cell mobilization and imbalanced regulation of metalloproteinases. Several candidates for nutraceutical supplementation in HF, such as CoQ10, grape seed extract, Olea Europea L- related antioxidants, SGLT2 inhibitors-rich apple extract and bergamot polyphenolic fraction have been assessed for their potential contribution to cardiomyocyte prottection. This approach should define the optimal approach for more targeted and successful strategies based on the use of nutraceuticals in HF to be confirmed by means of clinical trials exploring efficacy and safety of these compounds.

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Natural Products Targeting ER Stress, and the Functional Link to Mitochondria

Cited by 78 publications

References 61 publications

SARS-CoV-2: From the pathogenesis to potential anti-viral treatments

SARS-CoV-2: From the pathogenesis to potential anti-viral treatments

Pathophysiological Basis for Nutraceutical Supplementation in Heart Failure: A Comprehensive Review

Pathophysiological Basis for Nutraceutical Supplementation in Heart Failure: A Comprehensive Review

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