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Regulation of Autophagy in Cardiovascular Diseases by Natural Products.
Gu, S, Li, X
Advances in experimental medicine and biology. 2020;:731-736
Abstract
Several major cardiovascular diseases, such as heart failure (HF) and atherosclerosis (AS), have been linked to autophagy dysfunction. The influence of autophagy on the occurrence and development of cardiovascular diseases has two sides. Generally, the induction of autophagy at a low level can provide energy and nutrients for cells through degradation of damaged organelles, protect cardiomyocytes and vascular endothelial cells, and stabilize atherosclerotic plaques. However, excessive autophagy may damage cardiomyocytes and vascular endothelial cells and even cause cell death. Therefore, the study on the role and mechanism of autophagy in the pathogenesis of cardiovascular diseases may not only provide new targets for the treatment of cardiac remodeling, myocardial ischemia and reperfusion injury, atherosclerosis and heart failure, but also provide clues for the developing new drugs on prevention and treatment of clinical cardiovascular diseases. In this chapter, we reviewed the research progress on resveratrol, curcumin, epigallocatechin-3-gallate, and cordyceps sinensis on their recent research progress for cardiovascular diseases. Regulating autophagy may be an effective strategy for the treatment of cardiovascular diseases in the future.
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MCOLN1/TRPML1 inhibition - a novel strategy used by Helicobacter pylori to escape autophagic killing and antibiotic eradication therapy in vivo.
Capurro, MI, Prashar, A, Jones, NL
Autophagy. 2020;(1):169-170
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Abstract
Inhibition of host macroautophagy/autophagy is one of the strategies used by several intracellular pathogens, including H. pylori, to escape killing. Here we discuss our recent work that revealed the novel mechanism by which the vacuolating cytotoxin A (VacA) produced by H. pylori inhibits lysosomal and autophagic killing. We discovered that VacA impairs the activity of the lysosomal calcium channel MCOLN1/TRPML1 leading to the formation of enlarged, dysfunctional lysosomes and autophagosomes that serve as an intracellular niche, which allows the bacteria to escape eradication therapy.
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Therapeutic effects of kaempferol affecting autophagy and endoplasmic reticulum stress.
Ashrafizadeh, M, Tavakol, S, Ahmadi, Z, Roomiani, S, Mohammadinejad, R, Samarghandian, S
Phytotherapy research : PTR. 2020;(5):911-923
Abstract
Regulated cell death (RCD) guarantees to preserve organismal homeostasis. Apoptosis and autophagy are two major arms of RCD, while endoplasmic reticulum (ER) as a crucial organelle involved in proteostasis, promotes cells toward autophagy and apoptosis. Alteration in ER stress and autophagy machinery is responsible for a great number of diseases. Therefore, targeting those pathways appears to be beneficial in the treatment of relevant diseases. Meantime, among the traditional herb medicine, kaempferol as a flavonoid seems to be promising to modulate ER stress and autophagy and exhibits protective effects on malfunctioning cells. There are some reports indicating the capability of kaempferol in affecting autophagy and ER stress. In brief, kaempferol modulates autophagy in noncancerous cells to protect cells against malfunction, while it induces cell mortality derived from autophagy through the elevation of p-AMP-activated protein kinase, light chain-3-II, autophagy-related geness, and Beclin-1 in cancer cells. Noteworthy, kaempferol enhances cell survival through C/EBP homologous protein (CHOP) suppression and GRP78 increment in noncancerous cells, while it enhances cell mortality through the induction of unfolding protein response and CHOP increment in cancer cells. In this review, we discuss how kaempferol modulates autophagy and ER stress in noncancer and cancer cells to expand our knowledge of new pharmacological compounds for the treatment of associated diseases.
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The Prospects of Therapeutic Potential and Drug Development Targeting Autophagy in Cancer.
Bao, J, Liu, B, Wu, C
Advances in experimental medicine and biology. 2020;:663-679
Abstract
Autophagy is a self-protection mechanism of cells. Cells can degrade damaged organelles and macromolecules in this way to guarantee the growth and development of cells. In recent years, more and more researches have found that autophagy also plays a certain role in the occurrence and development of tumors. The dual role of autophagy in the development of tumors includes inhibiting the development of tumors; meanwhile, under the condition of insufficient nutrition, autophagy degrades organelles to reduce oxidative stress and provide nutrition and energy for tumor cells so as to protect tumor cells. The regulation of autophagy depends on the development of the tumor, and the corresponding autophagy inducers or inhibitors are constantly emerging, which provides a new direction for tumor treatment.
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Regulation of Autophagy in Neurodegenerative Diseases by Natural Products.
Liu, S, Li, X
Advances in experimental medicine and biology. 2020;:725-730
Abstract
Neurodegenerative diseases mainly include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD). It is now found that these diseases may be related to autophagic dysfunction. The mechanism is due to abnormalities in autophagy, which lead to abnormal or misfolded proteins accumulating in the cytoplasm, nucleus, and extracellular inclusion bodies, causing neuronal organelle damage and synaptic dysfunction. Since these diseases are much complex, the effect of monotherapy is not significantly affected. There is still a need to strengthen the study of anti-neurodegenerative drugs. Natural products should be a good source for the new drug discovery since most of natural products are multiple-target compounds. In this chapter, we reviewed some progress on studying resveratrol, curcumin, tripterine, and paeoniflorin. These natural products can eliminate abnormal protein aggregates by regulating autophagy, and thereby these compounds are promising to be used in prevention and treatment of neurodegenerative diseases in the future.
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Autophagy-related MicroRNAs in chronic lung diseases and lung cancer.
Rezaei, S, Mahjoubin-Tehran, M, Aghaee-Bakhtiari, SH, Jalili, A, Movahedpour, A, Khan, H, Moghoofei, M, Shojaei, Z, R Hamblin, M, Mirzaei, H
Critical reviews in oncology/hematology. 2020;:103063
Abstract
Chronic lung disease has become a leading cause of death in recent years. Despite several attempts to discover and develop new therapeutic approaches, patients often suffer a poor quality of life, and are faced with an increased risk of developing lung cancer. Lung cancer often occurs as an end-stage after years of chronic lung disease. An increased understanding of the pathophysiology of chronic lung disease may be obtained from studying the role of autophagy in its initiation and progression. MicroRNAs (miRNAs) play a critical role in the modulation of autophagy, and their deregulation could be associated with the initiation and progression of several chronic lung diseases. Herein, we documented that up/down regulation of miRNAs can activate or inhibit autophagy in chronic lung diseases including lung cancer. Therefore, theses miRNAs could be a promising therapeutic tool for lung cancer specially in drug-resistance lung cancer cells.
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Docosahexaenoic Acid, a Potential Treatment for Sarcopenia, Modulates the Ubiquitin-Proteasome and the Autophagy-Lysosome Systems.
Lee, JH, Jeon, JH, Lee, MJ
Nutrients. 2020;(9)
Abstract
One of the characteristic features of aging is the progressive loss of muscle mass, a nosological syndrome called sarcopenia. It is also a pathologic risk factor for many clinically adverse outcomes in older adults. Therefore, delaying the loss of muscle mass, through either boosting muscle protein synthesis or slowing down muscle protein degradation using nutritional supplements could be a compelling strategy to address the needs of the world's aging population. Here, we review the recently identified properties of docosahexaenoic acid (DHA). It was shown to delay muscle wasting by stimulating intermediate oxidative stress and inhibiting proteasomal degradation of muscle proteins. Both the ubiquitin-proteasome and the autophagy-lysosome systems are modulated by DHA. Collectively, growing evidence indicates that DHA is a potent pharmacological agent that could improve muscle homeostasis. Better understanding of cellular proteolytic systems associated with sarcopenia will allow us to identify novel therapeutic interventions, such as omega-3 polyunsaturated fatty acids, to treat this disease.
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Flavonoids as Anticancer Agents.
Kopustinskiene, DM, Jakstas, V, Savickas, A, Bernatoniene, J
Nutrients. 2020;(2)
Abstract
Flavonoids are polyphenolic compounds subdivided into 6 groups: isoflavonoids, flavanones, flavanols, flavonols, flavones and anthocyanidins found in a variety of plants. Fruits, vegetables, plant-derived beverages such as green tea, wine and cocoa-based products are the main dietary sources of flavonoids. Flavonoids have been shown to possess a wide variety of anticancer effects: they modulate reactive oxygen species (ROS)-scavenging enzyme activities, participate in arresting the cell cycle, induce apoptosis, autophagy, and suppress cancer cell proliferation and invasiveness. Flavonoids have dual action regarding ROS homeostasis-they act as antioxidants under normal conditions and are potent pro-oxidants in cancer cells triggering the apoptotic pathways and downregulating pro-inflammatory signaling pathways. This article reviews the biochemical properties and bioavailability of flavonoids, their anticancer activity and its mechanisms of action.
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Mechanisms Regulating the UPS-ALS Crosstalk: The Role of Proteaphagy.
Quinet, G, Gonzalez-Santamarta, M, Louche, C, Rodriguez, MS
Molecules (Basel, Switzerland). 2020;(10)
Abstract
Protein degradation is tightly regulated inside cells because of its utmost importance for protein homeostasis (proteostasis). The two major intracellular proteolytic pathways are the ubiquitin-proteasome and the autophagy-lysosome systems which ensure the fate of proteins when modified by various members of the ubiquitin family. These pathways are tightly interconnected by receptors and cofactors that recognize distinct chain architectures to connect with either the proteasome or autophagy under distinct physiologic and pathologic situations. The degradation of proteasome by autophagy, known as proteaphagy, plays an important role in this crosstalk since it favours the activity of autophagy in the absence of fully active proteasomes. Recently described in several biological models, proteaphagy appears to help the cell to survive when proteostasis is broken by the absence of nutrients or the excess of proteins accumulated under various stress conditions. Emerging evidence indicates that proteaphagy could be permanently activated in some types of cancer or when chemoresistance is observed in patients.
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10.
Autophagy in metabolic syndrome: breaking the wheel by targeting the renin-angiotensin system.
Menikdiwela, KR, Ramalingam, L, Rasha, F, Wang, S, Dufour, JM, Kalupahana, NS, Sunahara, KKS, Martins, JO, Moustaid-Moussa, N
Cell death & disease. 2020;(2):87
Abstract
Metabolic syndrome (MetS) is a complex, emerging epidemic which disrupts the metabolic homeostasis of several organs, including liver, heart, pancreas, and adipose tissue. While studies have been conducted in these research areas, the pathogenesis and mechanisms of MetS remain debatable. Lines of evidence show that physiological systems, such as the renin-angiotensin system (RAS) and autophagy play vital regulatory roles in MetS. RAS is a pivotal system known for controlling blood pressure and fluid balance, whereas autophagy is involved in the degradation and recycling of cellular components, including proteins. Although RAS is activated in MetS, the interrelationship between RAS and autophagy varies in glucose homeostatic organs and their cross talk is poorly understood. Interestingly, autophagy is attenuated in the liver during MetS, whereas autophagic activity is induced in adipose tissue during MetS, indicating tissue-specific discordant roles. We discuss in vivo and in vitro studies conducted in metabolic tissues and dissect their tissue-specific effects. Moreover, our review will focus on the molecular mechanisms by which autophagy orchestrates MetS and the ways future treatments could target RAS in order to achieve metabolic homeostasis.