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Inflammatory Pathways in Neuro-Muscular Degeneration, Metabolic Syndromes, Cancer and Infection

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A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Cellular Biochemistry".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 20253

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Special Issue Editors

Dr. Irene Faenza

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Guest Editor

Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
Interests: osteosarcoma; signal transduction; nucleus; phosphoinositide signaling; cyclin D3; Akt; chemotherapeutic agents; differentiation; nuclear phosphoinositides
Special Issues, Collections and Topics in MDPI journals

Dr. William Blalock

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Guest Editor

"Luigi Luca Cavalli-Sforza" Institute of Molecular Genetics, National Research Council of Italy, 40136 Bologna, Italy
Interests: Inflammation; stress; nuclear signaling; acute leukemia; bone marrow failure disorders; osteosarcoma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Inflammation is a common factor of most pathological conditions (genetic and acquired) and has been shown to promote progression of the disease state, whether it be growth, invasion/migration and metastases in cancer or enhanced apoptosis and cell death in degenerative diseases. While multiple signal transduction pathways affecting inflammation have been reported (Jak-STAT, NF-κB and PI3K-AKT), it is still unclear whether inflammatory signaling is an underlying cause or a byproduct of the pathology, or possibly both. In addition, novel transcriptomic and proteomic studies have highlighted the presence of an underlying network of innate immune signaling pathways which are aberrantly activated during the disease state. This Special Issue on inflammatory signaling will emphasize research aimed at understanding the role of inflammatory/stress signaling in altering normal cellular processes (ribosome biognesis, alternative RNA splicing, transcription, translation) during disease development and progression, as well as how an alteration of these processes resulting from a somatic or inherited genetic mutation directly affects inflammatory/stress signaling. In addition, the potential of infectious agents (HBV, HCV, HIV, HSV, H. pylori, etc.) to stimulate innate immune/inflammatory pathways, thereby promoting secondary disease, will be explored. In this regard, we would like to invite review articles which address the issues stated above from both a bioinformatics (proteiomics, transcriptomics) and a basic biological approach (post-translational modification, biochemical/biological activity). In addition, any original research adding relevant information to the topic is highly encouraged.

Dr. Irene Faenza
Dr. William Blalock
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

signal transduction
RNA metabolism/alterative splicing (spliceopathies)
Ribosomeopathies
inflammation
stress (metabolic/environmental/infectious)
cancer
metabolic syndromes (diabetes mellitus)
neuro-musculodegenerative disease

Published Papers (6 papers)

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Research

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15 pages, 1374 KiB

Open AccessEditor’s ChoiceArticle

DYT-PRKRA Mutation P222L Enhances PACT’s Stimulatory Activity on Type I Interferon Induction

by Lauren S. Vaughn, Kenneth Frederick, Samuel B. Burnett, Nutan Sharma, D. Cristopher Bragg, Sarah Camargos, Francisco Cardoso and Rekha C. Patel

Biomolecules 2022, 12(5), 713; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12050713 - 17 May 2022

Cited by 2 | Viewed by 2733

Abstract

DYT-PRKRA (dystonia 16 or DYT-PRKRA) is caused by mutations in the PRKRA gene that encodes PACT, the protein activator of interferon (IFN)-induced double-stranded (ds) RNA-activated protein kinase (PKR). PACT participates in several cellular pathways, of which its role as a PKR activator protein during integrated stress response (ISR) is the best characterized. Previously, we have established that the DYT-PRKRA mutations cause enhanced activation of PKR during ISR to sensitize DYT-PRKRA cells to apoptosis. In this study, we evaluate if the most prevalent substitution mutation reported in DYT-PRKRA patients alters PACT’s functional role in induction of type I IFNs via the retinoic acid-inducible gene I (RIG-I) signaling. Our results indicate that the P222L mutation augments PACT’s ability to induce IFN β in response to dsRNA and the basal expression of IFN β and IFN-stimulated genes (ISGs) is higher in DYT-PRKRA patient cells compared to cells from the unaffected controls. Additionally, IFN β and ISGs are also induced at higher levels in DYT-PRKRA cells in response to dsRNA. These results offer a new avenue for investigations directed towards understanding the underlying molecular pathomechanisms in DYT-PRKRA. Full article

(This article belongs to the Special Issue Inflammatory Pathways in Neuro-Muscular Degeneration, Metabolic Syndromes, Cancer and Infection)

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22 pages, 3701 KiB

Open AccessEditor’s ChoiceArticle

APR-246—The Mutant TP53 Reactivator—Increases the Effectiveness of Berberine and Modified Berberines to Inhibit the Proliferation of Pancreatic Cancer Cells

by James Andrew McCubrey, Stephen L. Abrams, Linda S. Steelman, Lucio Cocco, Stefano Ratti, Alberto M. Martelli, Paolo Lombardi, Agnieszka Gizak and Przemysław Duda

Biomolecules 2022, 12(2), 276; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12020276 - 08 Feb 2022

Cited by 5 | Viewed by 2229

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer. In ~75% of PDAC, the tumor suppressor TP53 gene is mutated. Novel approaches to treat cancer involve compounds called mutant TP53 reactivators. They interact with mutant TP53 proteins and restore some of their growth suppressive properties, but they may also interact with other proteins, e.g., TP63 and TP73. We examined the ability of the TP53 reactivator APR-246 to interact with eleven modified berberine compounds (NAX compounds) in the presence and absence of WT-TP53 in two PDAC cell lines: the MIA-PaCa-2, which has gain of function (GOF) TP53 mutations on both alleles, and PANC-28, which lacks expression of the WT TP53 protein. Our results indicate the TP53 reactivator-induced increase in therapeutic potential of many modified berberines. Full article

(This article belongs to the Special Issue Inflammatory Pathways in Neuro-Muscular Degeneration, Metabolic Syndromes, Cancer and Infection)

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Review

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20 pages, 1082 KiB

Open AccessEditor’s ChoiceReview

Innate Immunity: A Balance between Disease and Adaption to Stress

by Irene Faenza and William L. Blalock

Biomolecules 2022, 12(5), 737; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12050737 - 23 May 2022

Cited by 7 | Viewed by 3541

Abstract

Since first being documented in ancient times, the relation of inflammation with injury and disease has evolved in complexity and causality. Early observations supported a cause (injury) and effect (inflammation) relationship, but the number of pathologies linked to chronic inflammation suggests that inflammation itself acts as a potent promoter of injury and disease. Additionally, results from studies over the last 25 years point to chronic inflammation and innate immune signaling as a critical link between stress (exogenous and endogenous) and adaptation. This brief review looks to highlight the role of the innate immune response in disease pathology, and recent findings indicating the innate immune response to chronic stresses as an influence in driving adaptation. Full article

(This article belongs to the Special Issue Inflammatory Pathways in Neuro-Muscular Degeneration, Metabolic Syndromes, Cancer and Infection)

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12 pages, 2124 KiB

Open AccessReview

Roles of PI3K/AKT/mTOR Axis in Arteriovenous Fistula

by Stefano Ratti, Raffaella Mauro, Cristina Rocchi, Sara Mongiorgi, Giulia Ramazzotti, Mauro Gargiulo, Lucia Manzoli, Lucio Cocco and Roberta Fiume

Biomolecules 2022, 12(3), 350; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12030350 - 23 Feb 2022

Cited by 2 | Viewed by 2259

Abstract

Renal failure is a worldwide disease with a continuously increasing prevalence and involving a rising need for long-term treatment, mainly by haemodialysis. Arteriovenous fistula (AVF) is the favourite type of vascular access for haemodialysis; however, the lasting success of this therapy depends on its maturation, which is directly influenced by many concomitant processes such as vein wall thickening or inflammation. Understanding the molecular mechanisms that drive AVF maturation and failure can highlight new or combinatorial drugs for more personalized therapy. In this review we analysed the relevance of critical enzymes such as PI3K, AKT and mTOR in processes such as wall thickening remodelling, immune system activation and inflammation reduction. We focused on these enzymes due to their involvement in the modulation of numerous cellular activities such as proliferation, differentiation and motility, and their impairment is related to many diseases such as cancer, metabolic syndrome and neurodegenerative disorders. In addition, these enzymes are highly druggable targets, with several inhibitors already being used in patient treatment for cancer and with encouraging results for AVF. Finally, we delineate how these enzymes may be targeted to control specific aspects of AVF in an effort to propose a more specialized therapy with fewer side effects. Full article

(This article belongs to the Special Issue Inflammatory Pathways in Neuro-Muscular Degeneration, Metabolic Syndromes, Cancer and Infection)

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31 pages, 7801 KiB

Open AccessReview

Essential Fatty Acids and Their Metabolites in the Pathobiology of Inflammation and Its Resolution

by Undurti N Das

Biomolecules 2021, 11(12), 1873; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11121873 - 14 Dec 2021

Cited by 51 | Viewed by 4846

Abstract

Arachidonic acid (AA) metabolism is critical in the initiation and resolution of inflammation. Prostaglandin E2 (PGE2) and leukotriene B4/D4/E4 (LTB4/LD4/LTE4), derived from AA, are involved in the initiation of inflammation and regulation of immune response, hematopoiesis, and M1 (pro-inflammatory) macrophage facilitation. Paradoxically, PGE2 suppresses interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production and triggers the production of lipoxin A4 (LXA4) from AA to initiate inflammation resolution process and augment regeneration of tissues. LXA4 suppresses PGE2 and LTs’ synthesis and action and facilitates M2 macrophage generation to resolve inflammation. AA inactivates enveloped viruses including SARS-CoV-2. Macrophages, NK cells, T cells, and other immunocytes release AA and other bioactive lipids to produce their anti-microbial actions. AA, PGE2, and LXA4 have cytoprotective actions, regulate nitric oxide generation, and are critical to maintain cell shape and control cell motility and phagocytosis, and inflammation, immunity, and anti-microbial actions. Hence, it is proposed that AA plays a crucial role in the pathobiology of ischemia/reperfusion injury, sepsis, COVID-19, and other critical illnesses, implying that its (AA) administration may be of significant benefit in the prevention and amelioration of these diseases. Full article

(This article belongs to the Special Issue Inflammatory Pathways in Neuro-Muscular Degeneration, Metabolic Syndromes, Cancer and Infection)

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17 pages, 2188 KiB

Open AccessEditor’s ChoiceReview

How Inflammation Pathways Contribute to Cell Death in Neuro-Muscular Disorders

by Sara Salucci, Anna Bartoletti Stella, Michela Battistelli, Sabrina Burattini, Alberto Bavelloni, Lucio Ildebrando Cocco, Pietro Gobbi and Irene Faenza

Biomolecules 2021, 11(8), 1109; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11081109 - 28 Jul 2021

Cited by 7 | Viewed by 3538

Abstract

Neuro-muscular disorders include a variety of diseases induced by genetic mutations resulting in muscle weakness and waste, swallowing and breathing difficulties. However, muscle alterations and nerve depletions involve specific molecular and cellular mechanisms which lead to the loss of motor-nerve or skeletal-muscle function, often due to an excessive cell death. Morphological and molecular studies demonstrated that a high number of these disorders seem characterized by an upregulated apoptosis which significantly contributes to the pathology. Cell death involvement is the consequence of some cellular processes that occur during diseases, including mitochondrial dysfunction, protein aggregation, free radical generation, excitotoxicity and inflammation. The latter represents an important mediator of disease progression, which, in the central nervous system, is known as neuroinflammation, characterized by reactive microglia and astroglia, as well the infiltration of peripheral monocytes and lymphocytes. Some of the mechanisms underlying inflammation have been linked to reactive oxygen species accumulation, which trigger mitochondrial genomic and respiratory chain instability, autophagy impairment and finally neuron or muscle cell death. This review discusses the main inflammatory pathways contributing to cell death in neuro-muscular disorders by highlighting the main mechanisms, the knowledge of which appears essential in developing therapeutic strategies to prevent the consequent neuron loss and muscle wasting. Full article

(This article belongs to the Special Issue Inflammatory Pathways in Neuro-Muscular Degeneration, Metabolic Syndromes, Cancer and Infection)

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