The Natural Occurring Compounds Targeting Endoplasmic Reticulum Stress

Liu, Hai; Yang, Jiajun; Li, Linfu; Shi, Weimei; Yuan, Xiaoliang; Wu, Longhuo

doi:10.1155/2016/7831282

Cited by 42 publications

(32 citation statements)

References 136 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tailoring the natural products to enhance their potency, availability, selectivity and various other properties have introduced several clinically therapeutic drugs 21 – 24 . Liu et al ., have described several naturally occurring saponins, alkaloids and polyphenols that regulate ER stress induced cell death via apoptosis and autophagy 25 . Alternatively, flavonoids are natural antioxidants that have been reported to exert neuroprotective functions in several cell lines and in vivo models 26 , 27 .…”

Section: Introductionmentioning

confidence: 99%

Kaempferol mitigates Endoplasmic Reticulum Stress Induced Cell Death by targeting caspase 3/7

Abdullah

Ravanan

2018

Sci Rep

View full text Add to dashboard Cite

The Endoplasmic Reticulum (ER) plays a fundamental role in executing multiple cellular processes required for normal cellular function. Accumulation of misfolded/unfolded proteins in the ER triggers ER stress which contributes to progression of multiple diseases including neurodegenerative disorders. Recent reports have shown that ER stress inhibition could provide positive response against neuronal injury, ischemia and obesity in in vivo models. Our search towards finding an ER stress inhibitor has led to the functional discovery of kaempferol, a phytoestrogen possessing ER stress inhibitory activity in cultured mammalian cells. We have shown that kaempferol pre-incubation significantly inhibits the expression of GRP78 (a chaperone) and CHOP (ER stress associated pro-apoptotic transcription factor) under stressed condition. Also, our investigation in the inhibitory specificity of kaempferol has revealed that it inhibits cell death induced by diverse stimuli. Further study on exploring the molecular mechanism implied that kaempferol renders protection by targeting caspases. Both the in silico docking and in vitro assay using recombinant caspase-3 enzyme confirmed the binding of kaempferol to caspases, through an allosteric mode of competitive inhibition. Altogether, we have demonstrated the ability of kaempferol to alleviate ER stress in in vitro model.

show abstract

Section: Introductionmentioning

confidence: 99%

Kaempferol mitigates Endoplasmic Reticulum Stress Induced Cell Death by targeting caspase 3/7

Abdullah

Ravanan

2018

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Alteration of ER homeostasis may result in ER stress, which plays important roles in metabolism, inflammation, and tumorigenesis. ER stress is associated with several markers such as inositol-requiring enzyme-1 (IRE1), PKR-like ER kinase (PERK), activating transcription factor-6 (ATF6), X-box binding protein 1 (XBP1), CCAAT-enhancer-binding protein homologous protein (CHOP), and eukaryotic translation initiation factor 2 subunit alpha (eIF2α), which are involved to various degrees in multiple diseases [ 18 , 19 ]. ER is also responsible for Ca 2+ storage.…”

Section: Introductionmentioning

confidence: 99%

ER stress and subsequent activated calpain play a pivotal role in skeletal muscle wasting after severe burn injury

Chu

Chai

et al. 2017

PLoS ONE

View full text Add to dashboard Cite

Severe burns are typically followed by hypermetabolism characterized by significant muscle wasting, which causes considerable morbidity and mortality. The aim of the present study was to explore the underlying mechanisms of skeletal muscle damage/wasting post-burn. Rats were randomized to the sham, sham+4-phenylbutyrate (4-PBA, a pharmacological chaperone promoting endoplasmic reticulum (ER) folding/trafficking, commonly considered as an inhibitor of ER), burn (30% total body surface area), and burn+4-PBA groups; and sacrificed at 1, 4, 7, 14 days after the burn injury. Tibial anterior muscle was harvested for transmission electron microscopy, calcium imaging, gene expression and protein analysis of ER stress / ubiquitin-proteasome system / autophagy, and calpain activity measurement. The results showed that ER stress markers were increased in the burn group compared with the sham group, especially at post-burn days 4 and 7, which might consequently elevate cytoplasmic calcium concentration, promote calpain production as well as activation, and cause skeletal muscle damage/wasting of TA muscle after severe burn injury. Interestingly, treatment with 4-PBA prevented burn-induced ER swelling and altered protein expression of ER stress markers and calcium release, attenuating calpain activation and skeletal muscle damage/wasting after severe burn injury. Atrogin-1 and LC3-II/LC3-I ratio were also increased in the burn group compared with the sham group, while MuRF-1 remained unchanged; 4-PBA decreased atrogin-1 in the burn group. Taken together, these findings suggested that severe burn injury induces ER stress, which in turns causes calpain activation. ER stress and subsequent activated calpain play a critical role in skeletal muscle damage/wasting in burned rats.

show abstract

“…ER homeostasis is essential for cell survival, but a broad range of pathological conditions may disrupt that cellular state and evoke the ER stress conditions. They are directly activated upon glucose deprivation, redox imbalance, calcium homeostasis disruption, and as a response to the accumulation of improperly folded proteins within the ER lumen [29,138]. Aggregation of unfolded and misfolded proteins within the ER and subsequent ER stress conditions trigger activation of the UPR signaling branches, which are responsible for enhanced ER ability for protein folding and attenuation of global protein translation [139].…”

Section: Er Stress and The Upr Signaling Branchesmentioning

confidence: 99%

The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases

Rozpędek‐Kamińska

Siwecka

Wawrzynkiewicz

et al. 2020

IJMS

View full text Add to dashboard Cite

Higher prevalence of neurodegenerative diseases is strictly connected with progressive aging of the world population. Interestingly, a broad range of age-related, neurodegenerative diseases is characterized by a common pathological mechanism—accumulation of misfolded and unfolded proteins within the cells. Under certain circumstances, such protein aggregates may evoke endoplasmic reticulum (ER) stress conditions and subsequent activation of the unfolded protein response (UPR) signaling pathways via the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-dependent manner. Under mild to moderate ER stress, UPR has a pro-adaptive role. However, severe or long-termed ER stress conditions directly evoke shift of the UPR toward its pro-apoptotic branch, which is considered to be a possible cause of neurodegeneration. To this day, there is no effective cure for Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), or prion disease. Currently available treatment approaches for these diseases are only symptomatic and cannot affect the disease progression. Treatment strategies, currently under detailed research, include inhibition of the PERK-dependent UPR signaling branches. The newest data have reported that the use of small-molecule inhibitors of the PERK-mediated signaling branches may contribute to the development of a novel, ground-breaking therapeutic approach for neurodegeneration. In this review, we critically describe all the aspects associated with such targeted therapy against neurodegenerative proteopathies.

show abstract

The Natural Occurring Compounds Targeting Endoplasmic Reticulum Stress

Cited by 42 publications

References 136 publications

Kaempferol mitigates Endoplasmic Reticulum Stress Induced Cell Death by targeting caspase 3/7

Kaempferol mitigates Endoplasmic Reticulum Stress Induced Cell Death by targeting caspase 3/7

ER stress and subsequent activated calpain play a pivotal role in skeletal muscle wasting after severe burn injury

The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases

Contact Info

Product

Resources

About