The Pathogenesis of Pancreatitis and the Role of Autophagy DOI Creative Commons
Ioannis Tsomidis, Argyro Voumvouraki, Elias Kouroumalis

et al.

Gastroenterology Insights, Journal Year: 2024, Volume and Issue: 15(2), P. 303 - 341

Published: April 22, 2024

The pathogenesis of acute and chronic pancreatitis has recently evolved as new findings demonstrate a complex mechanism operating through various pathways. In this review, the current evidence indicating that several mechanisms act in concert to induce perpetuate were presented. As autophagy is now considered fundamental pathophysiology both pancreatitis, fundamentals pathway discussed allow for better understanding pathophysiological pancreatitis. aspects pathogenesis, including trypsinogen activation, ER stress mitochondrial dysfunction, implications inflammation, macrophage involvement innate immunity, well significance pancreatic stellate cells development fibrosis, also analyzed. Recent on exosomes miRNA regulatory role Finally, protection aggravation possible therapeutic reviewed.

Language: Английский

Mitochondrial Dysfunction and Chronic Liver Disease DOI Creative Commons

Chunyan Zhang,

Yabin Zhao,

Mengli Yu

et al.

Current Issues in Molecular Biology, Journal Year: 2022, Volume and Issue: 44(7), P. 3156 - 3165

Published: July 9, 2022

Mitochondria are generally considered the powerhouse of cell, a small subcellular organelle that produces most cellular energy in form adenosine triphosphate (ATP). In addition, mitochondria involved various biological functions, such as biosynthesis, lipid metabolism, oxidative phosphorylation, cell signal transduction, and apoptosis. Mitochondrial dysfunction is manifested different aspects, like increased mitochondrial reactive oxygen species (ROS), DNA (mtDNA) damage, (ATP) synthesis disorder, abnormal mitophagy, well changes morphology structure. related to occurrence development chronic liver diseases, including hepatocellular carcinoma (HCC), viral hepatitis, drug-induced injury (DILI), alcoholic fatty (AFL), non-alcoholic (NAFL). this review, we summarize discuss role mechanisms disease, focusing on discussing some latest studies disease.

Language: Английский

Citations

46
The relationship of alpha-synuclein to mitochondrial dynamics and quality control DOI Creative Commons
Naomi J. Thorne, David A. Tumbarello

Frontiers in Molecular Neuroscience, Journal Year: 2022, Volume and Issue: 15

Published: Aug. 26, 2022

Maintenance of mitochondrial health is essential for neuronal survival and relies upon dynamic changes in the network effective quality control mechanisms including mitochondrial-derived vesicle pathway mitophagy. Mitochondrial dysfunction has been implicated driving pathology several neurodegenerative diseases, Parkinson's disease (PD) where dopaminergic neurons substantia nigra are selectively degenerated. In addition, many genes with PD-associated mutations have defined functions organelle control, indicating that dysregulation may represent a key element pathology. The most well-characterized aspect PD relates to alpha-synuclein; an aggregation-prone protein forms intracellular Lewy-body inclusions. Details how alpha-synuclein exerts its toxicity not completely known, however, dysfunctional mitochondria observed both patients models Accordingly, association between function established. This alpha-synuclein's role transport, dynamics, control. Despite these relationships, there limited research defining direct linking dynamics this review, we will discuss current literature addressing provide insight into proposed promoting functional relationships. We also consider some alternative speculate what relationship might mean physiologically relation PD.

Language: Английский

Citations

40
The Role of Autophagy for the Regeneration of the Aging Liver DOI Open Access
Fengming Xu, Chuanfeng Hua, Hans‐Michael Tautenhahn

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(10), P. 3606 - 3606

Published: May 20, 2020

Age is one of the key risk factors to develop malignant diseases leading a high incidence hepatic tumors in elderly population. The only curative treatment for surgical removal, which initiates liver regeneration. However, regeneration impaired with aging, an increased patient. Due risk, those patients are potentially excluded from surgery. Aging impairs autophagy via lipofuscin accumulation and inhibition autophagosome formation. Autophagy recycling mechanism eukaryotic cells maintain homeostasis. Its principal function degrade endogenous bio-macromolecules cellular substances. A number recent studies have shown that reduced regenerative capacity aged remnant can be restored by promoting autophagy. activated multiple mTOR-dependent mTOR-independent pathways. inducing through pathway alone severely In contrast, observations suggest pathways might promising Conclusion: Activation inducer potential therapy regeneration, especially at risk.

Language: Английский

Citations

53
Autophagy in liver diseases DOI Open Access

Elias Kouroumalis,

Argryro Voumvouraki,

Aikaterini Augoustaki

et al.

World Journal of Hepatology, Journal Year: 2021, Volume and Issue: 13(1), P. 6 - 65

Published: Jan. 26, 2021

Autophagy is the liver cell energy recycling system regulating a variety of homeostatic mechanisms. Damaged organelles, lipids and proteins are degraded in lysosomes their elements re-used by cell. Investigations on autophagy have led to award two Nobel Prizes health important reports. In this review we describe fundamental functions including new data regulation autophagy. Moreover emphasize fact that acts like edge sword many occasions with most prominent paradigm being its involvement initiation progress hepatocellular carcinoma. We also focused implication specialized forms lipophagy mitophagy pathogenesis various diseases. analyzed not only well studied diseases, alcoholic nonalcoholic fatty fibrosis but viral hepatitis, biliary autoimmune hepatitis rare diseases inherited metabolic acetaminophene hepatotoxicity. stressed different consequences activation or impairment may hepatocytes as opposed Kupffer cells, sinusoidal endothelial cells hepatic stellate cells. Finally, limited clinical compared extensive experimental evidence possible future therapeutic interventions based manipulation.

Language: Английский

Citations

52
The pathogenesis and therapeutic strategies of heat stroke-induced liver injury DOI Creative Commons
Fuquan Wang, Yan Zhang, Jianhua Li

et al.

Critical Care, Journal Year: 2022, Volume and Issue: 26(1)

Published: Dec. 17, 2022

Abstract Heat stroke (HS) is a life-threatening systemic disease characterized by an elevated core body temperature of more than 40 ℃ and subsequent multiple organ dysfunction syndrome. With the growing frequency global heatwaves, incidence rate HS has increased significantly, which caused huge burden on people's lives health. Liver injury well-documented complication usually constitutes direct cause patient death. In recent years, lot research been carried out pathogenesis treatment strategies HS-induced liver injury. this review, we summarized important that confirmed so far. addition to comprehensive effect factors such as heat cytotoxicity, coagulopathy, inflammatory response syndrome, excessive hepatocyte cell pyroptosis, Kupffer cells, abnormal expression shock protein expression, other are also involved in Furthermore, have established current therapeutic for Our study great significance promoting understanding

Language: Английский

Citations

37
Emerging mechanistic insights of selective autophagy in hepatic diseases DOI Creative Commons
Md. Abdul Alim Al‐Bari, Yuko Ito, Paul G. Thomes

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 16, 2023

Macroautophagy (hereafter referred to as autophagy), a highly conserved metabolic process, regulates cellular homeostasis by degrading dysfunctional cytosolic constituents and invading pathogens via the lysosomal system. In addition, autophagy selectively recycles specific organelles such damaged mitochondria ( mitophagy), lipid droplets (LDs; lipophagy) or eliminates specialized intracellular pathogenic microorganisms hepatitis B virus (HBV) coronaviruses virophagy). Selective autophagy, particularly mitophagy, plays key role in preservation of healthy liver physiology, its dysfunction is connected pathogenesis wide variety diseases. For example, lipophagy has emerged defensive mechanism against chronic There prominent for mitophagy hepatic pathologies including non-alcoholic fatty disease (NAFLD), hepatocellular carcinoma (HCC), drug-induced injury. Moreover, these selective pathways virophagy are being investigated context viral and, more recently, coronavirus 2019 (COVID-19)-associated pathologies. The interplay between diverse types impact on diseases briefly addressed. Thus, modulating (e.g., mitophagy) would seem be effective improving Considering prominence this review summarizes current understanding molecular mechanisms functions (mainly physiology pathophysiology. This may help finding therapeutic interventions targeting manipulation autophagy.

Language: Английский

Citations

21
Therapeutic implications of targeting autophagy and TGF-β crosstalk for the treatment of liver fibrosis DOI
Samaneh Siapoush, Ramazan Rezaei, Helia Alavifard

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 329, P. 121894 - 121894

Published: June 27, 2023

Language: Английский

Citations

19
Natural Activators of Autophagy DOI

Julia A. Pavlova,

Ekaterina A. Guseva,

О. А. Донцова

et al.

Biochemistry (Moscow), Journal Year: 2024, Volume and Issue: 89(1), P. 1 - 26

Published: Jan. 1, 2024

Language: Английский

Citations

7
Cytosolic p53 Inhibits Parkin-Mediated Mitophagy and Promotes Acute Liver Injury Induced by Heat Stroke DOI Creative Commons
Wei Huang,

Weidang Xie,

Hanhui Zhong

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: May 13, 2022

Heat stroke (HS) is a severe condition characterized by increased morbidity and high mortality. Acute liver injury (ALI) well-documented complication of HS. The tumor suppressor p53 plays an important role in regulation mitochondrial integrity mitophagy several forms ALI. However, the p53-regulated HS-ALI remains unclear. In our study, we discovered dynamic changes hepatocytes demonstrated protective effects activation on HS-ALI. Pretreatment with 3-MA or Mdivi-1 significantly exacerbated ALI inhibiting mice. Consistent animal model results, silencing Parkin aggravated damage apoptosis HS-treated normal human cell line (LO2 cells). Moreover, described increase translocation from nucleus to cytoplasm, cytosolic binds LO2 cells following overexpression using specific adenovirus Tenovin-6 through Parkin-dependent both vivo vitro , whereas inhibition siRNA PFT-α effectively reversed this process. Our results demonstrate that inhibits preventing Parkin’s cytosol mitochondria, which decreases leads hepatocyte Overall, pharmacologic induction may be promising therapeutic approach for treatment.

Language: Английский

Citations

24
Peroxisome proliferator-activated receptors as targets to treat metabolic diseases: Focus on the adipose tissue, liver, and pancreas DOI Creative Commons
Henrique Souza-Tavares, Carolline Santos Miranda, Isabela Macedo Lopes Vasques‐Monteiro

et al.

World Journal of Gastroenterology, Journal Year: 2023, Volume and Issue: 29(26), P. 4136 - 4155

Published: July 6, 2023

The world is experiencing reflections of the intersection two pandemics: Obesity and coronavirus disease 2019. prevalence obesity has tripled since 1975 worldwide, representing substantial public health costs due to its comorbidities. adipose tissue initial site impairments. During excessive energy intake, it undergoes hyperplasia hypertrophy until overt inflammation insulin resistance turn adipocytes into dysfunctional cells that send lipotoxic signals other organs. pancreas one organs most affected by obesity. Once lipotoxicity becomes chronic, there an increase in secretion pancreatic beta cells, a surrogate for type 2 diabetes mellitus (T2DM). These alterations threaten survival islets, which tend become dysfunctional, reaching exhaustion long term. As liver, favors lipogenesis impairs beta-oxidation, resulting hepatic steatosis. This silent affects around 30% worldwide population can evolve end-stage liver disease. Although therapy steatosis remains be defined, peroxisome proliferator-activated receptors (PPARs) activation copes with T2DM management. Peroxisome PPARs are transcription factors found at several metabolic pathways, leading relief, improved thermogenesis, expressive mitigation increasing mitochondrial beta-oxidation. review aimed update potential PPAR agonists as targets treat diseases, focusing on plasticity remodeling.

Language: Английский

Citations

16