Cystic Fibrosis Defective Response to Infection Involves Autophagy and Lipid Metabolism

Mingione, Alessandra; Ottaviano, Emerenziana; Barcella, Matteo; Merelli, Ivan; Rosso, Lorenzo; Armeni, Tatiana; Cirilli, N.; Ghidoni, Riccardo; Borghi, Elisa; Signorelli, Paola

doi:10.3390/cells9081845

Cited by 9 publications

(8 citation statements)

References 80 publications

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“…Indeed, we showed that Myr promotes a TFEB-induced stress response. TFEB initiates a transcriptional program that reduces inflammation and oxidative stress, induces autophagy [ 45 , 51 ], organizes cellular lipids by increasing their oxidation [ 45 , 51 , 52 ] but also by favoring lipid storage formation [ 8 ]. These activities all contribute to reducing most of the cellular lipid species [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Ceramide Synthesis Reduces α-Synuclein Proteinopathy in a Cellular Model of Parkinson’s Disease

Mingione

Pivari

Plotegher

et al. 2021

IJMS

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Parkinson’s disease (PD) is a proteinopathy associated with the aggregation of α-synuclein and the formation of lipid–protein cellular inclusions, named Lewy bodies (LBs). LB formation results in impaired neurotransmitter release and uptake, which involve membrane traffic and require lipid synthesis and metabolism. Lipids, particularly ceramides, are accumulated in postmortem PD brains and altered in the plasma of PD patients. Autophagy is impaired in PD, reducing the ability of neurons to clear protein aggregates, thus worsening stress conditions and inducing neuronal death. The inhibition of ceramide synthesis by myriocin (Myr) in SH-SY5Y neuronal cells treated with preformed α-synuclein fibrils reduced intracellular aggregates, favoring their sequestration into lysosomes. This was associated with TFEB activation, increased expression of TFEB and LAMP2, and the cytosolic accumulation of LC3II, indicating that Myr promotes autophagy. Myr significantly reduces the fibril-related production of inflammatory mediators and lipid peroxidation and activates NRF2, which is downregulated in PD. Finally, Myr enhances the expression of genes that control neurotransmitter transport (SNARE complex, VMAT2, and DAT), whose progressive deficiency occurs in PD neurodegeneration. The present study suggests that counteracting the accumulation of inflammatory lipids could represent a possible therapeutic strategy for PD.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Ceramide Synthesis Reduces α-Synuclein Proteinopathy in a Cellular Model of Parkinson’s Disease

Mingione

Pivari

Plotegher

et al. 2021

IJMS

Self Cite

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“…Additionally, evidence suggests that the airway tract microbiota, thick secretions, and autophagy induction in CF patients may play a protective role against viral infections. Autophagy, as an immune mechanism in CF disease, could be heightened and actively contributes to the antiviral response (van Ewijk et al, 2005 ; Junkins et al, 2014 ; Mingione et al, 2020 ; Pehote and Vij, 2020 ).…”

Section: Replication Of Sarscov-2; Outcome In Cf Patientsmentioning

confidence: 99%

Occurrence of COVID-19 in cystic fibrosis patients: a review

Abolhasani,

Moein,

Rezaie

et al. 2024

Front. Microbiol.

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Cystic fibrosis (CF) is a genetic ailment caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This autosomal recessive disorder is characterized by diverse pathobiological abnormalities, such as the disorder of CFTR channels in mucosal surfaces, caused by inadequate clearance of mucus and sputum, in addition to the malfunctioning of mucous organs. However, the primary motive of mortality in CF patients is pulmonary failure, which is attributed to the colonization of opportunistic microorganisms, formation of resistant biofilms, and a subsequent decline in lung characteristics. In December 2019, the World Health Organization (WHO) declared the outbreak of the radical coronavirus disease 2019 (COVID-19) as a worldwide public health crisis, which unexpectedly spread not only within China but also globally. Given that the respiration system is the primary target of the COVID-19 virus, it is crucial to investigate the impact of COVID-19 on the pathogenesis and mortality of CF patients, mainly in the context of acute respiratory distress syndrome (ARDS). Therefore, the goal of this review is to comprehensively review the present literature on the relationship between cystic fibrosis, COVID-19 contamination, and development of ARDS. Several investigations performed during the early stages of the virus outbreak have discovered unexpected findings regarding the occurrence and effectiveness of COVID-19 in individuals with CF. Contrary to initial expectancies, the rate of infection and the effectiveness of the virus in CF patients are lower than those in the overall population. This finding may be attributed to different factors, including the presence of thick mucus, social avoidance, using remedies that include azithromycin, the fairly younger age of CF patients, decreased presence of ACE-2 receptors, and the effect of CFTR channel disorder on the replication cycle and infectivity of the virus. However, it is important to notice that certain situations, which include undergoing a transplant, can also doubtlessly boost the susceptibility of CF patients to COVID-19. Furthermore, with an increase in age in CF patients, it is vital to take into account the prevalence of the SARS-CoV-2 virus in this population. Therefore, ordinary surveillance of CF patients is vital to evaluate and save the population from the capability of transmission of the virus given the various factors that contribute to the spread of the SARS-CoV-2 outbreak in this precise organization.

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“…DHA, like other long-chain n-3 fatty acids, are alo transferred to special pro-solving lipid mediators (SPM), e.g., the resolvins, maresins and protectins, of importance to balance inflammation provided by the ARA metabolites [94]. The role of SPM in regulating autophagy, which is defective in CF, may be a possible therapeutic option against 136 the persistent inflammation [95][96][97]. That was supported by adding resolvin D1 to infected CF KO mice and in studies of cells from CF patients [98].…”

Section: Fatty Acid Abnormalities In Cfmentioning

confidence: 99%

Nutrition in Cystic Fibrosis—Some Notes on the Fat Recommendations

Strandvik

2022

Nutrients

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Nutrition is important in cystic fibrosis (CF) because the disease is associated with a higher energy consumption, special nutritional deficiencies, and malabsorption mainly related to pancreatic insufficiency. The clinical course with deterioration of lung function has been shown to relate to nutrition. Despite general recommendation of high energy intake, the clinical deterioration is difficult to restrain suggesting that special needs have not been identified and specified. It is well-known that the CF phenotype is associated with lipid abnormalities, especially in the essential or conditionally essential fatty acids. This review will concentrate on the qualitative aspects of fat metabolism, which has mainly been neglected in dietary fat recommendations focusing on fat quantity. For more than 60 years it has been known and confirmed that the patients have a deficiency of linoleic acid, an n-6 essential fatty acid of importance for membrane structure and function. The ratio between arachidonic acid and docosahexaenoic acid, conditionally essential fatty acids of the n-6 and n-3 series, respectively, is often increased. The recently discovered relations between the CFTR modulators and lipid metabolism raise new interests in this field and together with new technology provide possibilities to specify further specify personalized therapy.

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Cystic Fibrosis Defective Response to Infection Involves Autophagy and Lipid Metabolism

Cited by 9 publications

References 80 publications

Inhibition of Ceramide Synthesis Reduces α-Synuclein Proteinopathy in a Cellular Model of Parkinson’s Disease

Inhibition of Ceramide Synthesis Reduces α-Synuclein Proteinopathy in a Cellular Model of Parkinson’s Disease

Occurrence of COVID-19 in cystic fibrosis patients: a review

Nutrition in Cystic Fibrosis—Some Notes on the Fat Recommendations

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