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Proteomes, Volume 12, Issue 1 (March 2024) – 9 articles

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14 pages, 768 KiB  
Review
Proteoform Analysis of the Human Olfactory System: A Window into Neurodegenerative Diseases
by Eqrem Rusi, Fiorenza Pennacchia, Wael Abu Ruqa, Giuseppina Talarico, Giuseppe Bruno, Antonio Minni and Christian Barbato
Proteomes 2024, 12(1), 9; https://0-doi-org.brum.beds.ac.uk/10.3390/proteomes12010009 - 21 Mar 2024
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Abstract
Background: Very little is known about the proteome of the human olfactory system and how diseases associated with olfactory dysfunctions can affect it. With this review, we try to summarize the existing literature on the use of this technique for a better [...] Read more.
Background: Very little is known about the proteome of the human olfactory system and how diseases associated with olfactory dysfunctions can affect it. With this review, we try to summarize the existing literature on the use of this technique for a better understanding of the neurodegenerative disease process. Methods: We used the PubMed database and found different articles which were then selected independently by three authors. Results: We found 157 articles, of which, after careful selection, only 30 were analyzed in this review. We presented all the associations identified between the protein/pathway alterations neurodegenerative diseases and SARS-CoV-2 infection. Conclusions: We think that the proteome of the olfactory system through blood, saliva, and mucus analysis could be a new way to better understand, diagnose, and finally treat neurodegenerative diseases. Full article
(This article belongs to the Topic Proteomics and Metabolomics in Biomedicine, 2nd Volume)
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19 pages, 1241 KiB  
Review
Biomarkers in Ovarian Cancer: Towards Personalized Medicine
by Carlos López-Portugués, María Montes-Bayón and Paula Díez
Proteomes 2024, 12(1), 8; https://0-doi-org.brum.beds.ac.uk/10.3390/proteomes12010008 - 18 Mar 2024
Cited by 1 | Viewed by 2095
Abstract
Ovarian cancer is one of the deadliest cancers in women. The lack of specific symptoms, especially at the initial stages of disease development, together with the malignancy heterogeneity, lower the life expectancy of patients. Aiming to improve survival rates, diagnostic and prognostic biomarkers [...] Read more.
Ovarian cancer is one of the deadliest cancers in women. The lack of specific symptoms, especially at the initial stages of disease development, together with the malignancy heterogeneity, lower the life expectancy of patients. Aiming to improve survival rates, diagnostic and prognostic biomarkers are increasingly employed in clinics, providing gynecologists and oncologists with new tools to guide their treatment decisions. Despite the vast number of investigations, there is still an urgent need to discover more ovarian cancer subtype-specific markers which could further improve patient classification. To this end, high-throughput screening technologies, like mass spectrometry, are applied to deepen the tumoral cellular landscape and describe the malignant phenotypes. As for disease treatment, new targeted therapies, such as those based on PARP inhibitors, have shown great efficacy in destroying the tumoral cells. Likewise, drug-nanocarrier systems targeting the tumoral cells have exhibited promising results. In this narrative review, we summarize the latest achievements in the pursuit of biomarkers for ovarian cancer and recent anti-tumoral therapies. Full article
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19 pages, 7120 KiB  
Article
Quantitative Proteomics Reveal Region-Specific Alterations in Neuroserpin-Deficient Mouse Brain and Retina: Insights into Serpini1 Function
by Shahab Mirshahvaladi, Nitin Chitranshi, Ardeshir Amirkhani, Rashi Rajput, Devaraj Basavarajappa, Roshana Vander Wall, Dana Pascovici, Angela Godinez, Giovanna Galliciotti, Joao A. Paulo, Veer Gupta, Stuart L. Graham, Vivek Gupta and Mehdi Mirzaei
Proteomes 2024, 12(1), 7; https://0-doi-org.brum.beds.ac.uk/10.3390/proteomes12010007 - 14 Mar 2024
Viewed by 1870
Abstract
Neural regeneration and neuroprotection represent strategies for future management of neurodegenerative disorders such as Alzheimer’s disease (AD) or glaucoma. However, the complex molecular mechanisms that are involved in neuroprotection are not clearly understood. A promising candidate that maintains neuroprotective signaling networks is neuroserpin [...] Read more.
Neural regeneration and neuroprotection represent strategies for future management of neurodegenerative disorders such as Alzheimer’s disease (AD) or glaucoma. However, the complex molecular mechanisms that are involved in neuroprotection are not clearly understood. A promising candidate that maintains neuroprotective signaling networks is neuroserpin (Serpini1), a serine protease inhibitor expressed in neurons which selectively inhibits extracellular tissue-type plasminogen activator (tPA)/plasmin and plays a neuroprotective role during ischemic brain injury. Abnormal function of this protein has been implicated in several conditions including stroke, glaucoma, AD, and familial encephalopathy with neuroserpin inclusion bodies (FENIB). Here, we explore the potential biochemical roles of Serpini1 by comparing proteome changes between neuroserpin-deficient (NS−/−) and control mice, in the retina (RE), optic nerve (ON), frontal cortex (FC), visual cortex (VC), and cerebellum (CB). To achieve this, a multiple-plex quantitative proteomics approach using isobaric tandem mass tag (TMT) technology was employed followed by functional enrichment and protein–protein interaction analysis. We detected around 5000 proteins in each tissue and a pool of 6432 quantified proteins across all regions, resulting in a pool of 1235 differentially expressed proteins (DEPs). Principal component analysis and hierarchical clustering highlighted similarities and differences in the retina compared to various brain regions, as well as differentiating NS−/− proteome signatures from control samples. The visual cortex revealed the highest number of DEPs, followed by cerebellar regions. Pathway analysis unveiled region-specific changes, including visual perception, focal adhesion, apoptosis, glutamate receptor activation, and supramolecular fiber organization in RE, ON, FC, VC, and CB, respectively. These novel findings provide comprehensive insights into the region-specific networking of Serpini1 in the central nervous system, further characterizing its potential role as a neuroprotective agent. Data are available via ProteomeXchange with identifier PXD046873. Full article
(This article belongs to the Special Issue Quantitative Proteomics: Techniques and Applications)
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14 pages, 2376 KiB  
Article
Observations from the Proteomics Bench
by Simone König, Karin Schork and Martin Eisenacher
Proteomes 2024, 12(1), 6; https://0-doi-org.brum.beds.ac.uk/10.3390/proteomes12010006 - 6 Feb 2024
Viewed by 1444
Abstract
Many challenges in proteomics result from the high-throughput nature of the experiments. This paper first presents pre-analytical problems, which still occur, although the call for standardization in omics has been ongoing for many years. This article also discusses aspects that affect bioinformatic analysis [...] Read more.
Many challenges in proteomics result from the high-throughput nature of the experiments. This paper first presents pre-analytical problems, which still occur, although the call for standardization in omics has been ongoing for many years. This article also discusses aspects that affect bioinformatic analysis based on three sets of reference data measured with different orbitrap instruments. Despite continuous advances in mass spectrometer technology as well as analysis software, data-set-wise quality control is still necessary, and decoy-based estimation, although challenged by modern instruments, should be utilized. We draw attention to the fact that numerous young researchers perceive proteomics as a mature, readily applicable technology. However, it is important to emphasize that the maximum potential of the technology can only be realized by an educated handling of its limitations. Full article
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14 pages, 2339 KiB  
Article
Enhanced Electrophoretic Depletion of Sodium Dodecyl Sulfate with Methanol for Membrane Proteome Analysis by Mass Spectrometry
by Hammam H. Said and Alan A. Doucette
Proteomes 2024, 12(1), 5; https://0-doi-org.brum.beds.ac.uk/10.3390/proteomes12010005 - 2 Feb 2024
Viewed by 1967
Abstract
Membrane proteins are underrepresented during proteome characterizations, primarily owing to their lower solubility. Sodium dodecyl sulfate (SDS) is favored to enhance protein solubility but interferes with downstream analysis by mass spectrometry. Here, we present an improved workflow for SDS depletion using transmembrane electrophoresis [...] Read more.
Membrane proteins are underrepresented during proteome characterizations, primarily owing to their lower solubility. Sodium dodecyl sulfate (SDS) is favored to enhance protein solubility but interferes with downstream analysis by mass spectrometry. Here, we present an improved workflow for SDS depletion using transmembrane electrophoresis (TME) while retaining a higher recovery of membrane proteins. Though higher levels of organic solvent lower proteome solubility, we found that the inclusion of 40% methanol provided optimal solubility of membrane proteins, with 86% recovery relative to extraction with SDS. Incorporating 40% methanol during the electrophoretic depletion of SDS by TME also maximized membrane protein recovery. We further report that methanol accelerates the rate of detergent removal, allowing TME to deplete SDS below 100 ppm in under 3 min. This is attributed to a three-fold elevation in the critical micelle concentration (CMC) of SDS in the presence of methanol, combined with a reduction in the SDS to protein binding ratio in methanol (0.3 g SDS/g protein). MS analysis of membrane proteins isolated from the methanol-assisted workflow revealed enhanced proteome detection, particularly for proteins whose pI contributed a minimal net charge and therefore possessed reduced solubility in a purely aqueous solvent. This protocol presents a robust approach for the preparation of membrane proteins by maximizing their solubility in MS-compatible solvents, offering a tool to advance membrane proteome characterization. Full article
(This article belongs to the Section Proteomics Technology and Methodology Development)
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41 pages, 4798 KiB  
Perspective
How Can Proteomics Help to Elucidate the Pathophysiological Crosstalk in Muscular Dystrophy and Associated Multi-System Dysfunction?
by Paul Dowling, Capucine Trollet, Elisa Negroni, Dieter Swandulla and Kay Ohlendieck
Proteomes 2024, 12(1), 4; https://0-doi-org.brum.beds.ac.uk/10.3390/proteomes12010004 - 16 Jan 2024
Cited by 1 | Viewed by 2493
Abstract
This perspective article is concerned with the question of how proteomics, which is a core technique of systems biology that is deeply embedded in the multi-omics field of modern bioresearch, can help us better understand the molecular pathogenesis of complex diseases. As an [...] Read more.
This perspective article is concerned with the question of how proteomics, which is a core technique of systems biology that is deeply embedded in the multi-omics field of modern bioresearch, can help us better understand the molecular pathogenesis of complex diseases. As an illustrative example of a monogenetic disorder that primarily affects the neuromuscular system but is characterized by a plethora of multi-system pathophysiological alterations, the muscle-wasting disease Duchenne muscular dystrophy was examined. Recent achievements in the field of dystrophinopathy research are described with special reference to the proteome-wide complexity of neuromuscular changes and body-wide alterations/adaptations. Based on a description of the current applications of top-down versus bottom-up proteomic approaches and their technical challenges, future systems biological approaches are outlined. The envisaged holistic and integromic bioanalysis would encompass the integration of diverse omics-type studies including inter- and intra-proteomics as the core disciplines for systematic protein evaluations, with sophisticated biomolecular analyses, including physiology, molecular biology, biochemistry and histochemistry. Integrated proteomic findings promise to be instrumental in improving our detailed knowledge of pathogenic mechanisms and multi-system dysfunction, widening the available biomarker signature of dystrophinopathy for improved diagnostic/prognostic procedures, and advancing the identification of novel therapeutic targets to treat Duchenne muscular dystrophy. Full article
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21 pages, 1969 KiB  
Review
The Mechanisms of Regulated Cell Death: Structural and Functional Proteomic Pathways Induced or Inhibited by a Specific Protein—A Narrative Review
by Diego Fernández-Lázaro, Begoña Sanz and Jesús Seco-Calvo
Proteomes 2024, 12(1), 3; https://0-doi-org.brum.beds.ac.uk/10.3390/proteomes12010003 - 5 Jan 2024
Cited by 1 | Viewed by 2125
Abstract
Billions of cells die in us every hour, and our tissues do not shrink because there is a natural regulation where Cell Death (CD) is balanced with cell division. The process in which cells eliminate themselves in a controlled manner is called Programmed [...] Read more.
Billions of cells die in us every hour, and our tissues do not shrink because there is a natural regulation where Cell Death (CD) is balanced with cell division. The process in which cells eliminate themselves in a controlled manner is called Programmed Cell Death (PCD). The PCD plays an important role during embryonic development, in maintaining homeostasis of the body’s tissues, and in the elimination of damaged cells, under a wide range of physiological and developmental stimuli. A multitude of protein mediators of PCD have been identified and signals have been found to utilize common pathways elucidating the proteins involved. This narrative review focuses on caspase-dependent and caspase-independent PCD pathways. Included are studies of caspase-dependent PCD such as Anoikis, Catastrophe Mitotic, Pyroptosis, Emperitosis, Parthanatos and Cornification, and Caspase-Independent PCD as Wallerian Degeneration, Ferroptosis, Paraptosis, Entosis, Methuosis, and Extracellular Trap Abnormal Condition (ETosis), as well as neutrophil extracellular trap abnormal condition (NETosis) and Eosinophil Extracellular Trap Abnormal Condition (EETosis). Understanding PCD from those reported in this review could shed substantial light on the processes of biological homeostasis. In addition, identifying specific proteins involved in these processes is mandatory to identify molecular biomarkers, as well as therapeutic targets. This knowledge could provide the ability to modulate the PCD response and could lead to new therapeutic interventions in a wide range of diseases. Full article
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13 pages, 285 KiB  
Review
Proteomics of Toxigenic Corynebacteria
by Andreas Burkovski
Proteomes 2024, 12(1), 2; https://0-doi-org.brum.beds.ac.uk/10.3390/proteomes12010002 - 30 Dec 2023
Cited by 1 | Viewed by 1866
Abstract
Within the genus Corynebacterium, six species are potential carriers of the tox gene, which encodes the highly potent diphtheria exotoxin: Corynebacterium diphtheriae, Corynebacterium belfantii, Corynebacterium rouxii, Corynebacterium ulcerans, Corynebacterium pseudotuberculosis and Corynebacterium silvaticum. Based on their potential to [...] Read more.
Within the genus Corynebacterium, six species are potential carriers of the tox gene, which encodes the highly potent diphtheria exotoxin: Corynebacterium diphtheriae, Corynebacterium belfantii, Corynebacterium rouxii, Corynebacterium ulcerans, Corynebacterium pseudotuberculosis and Corynebacterium silvaticum. Based on their potential to infect different host species and cause either human infections, zoonotic diseases or infections of economically important animals, these bacteria are of high scientific and economic interest and different research groups have carried out proteome analyses. These showed that especially the combination of MS-based proteomics with bioinformatic tools helped significantly to elucidate the functional aspects of corynebacterial genomes and to handle the genome and proteome complexity. The combination of proteomic and bioinformatic approaches was also used to discover new vaccine and drug targets. In addition, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has been established as a fast and precise tool for the identification of these bacteria. Full article
16 pages, 1443 KiB  
Review
Unveiling the Dichotomy of Urinary Proteins: Diagnostic Insights into Breast and Prostate Cancer and Their Roles
by Yan Feng, Qingji Huo, Bai-Yan Li and Hiroki Yokota
Proteomes 2024, 12(1), 1; https://0-doi-org.brum.beds.ac.uk/10.3390/proteomes12010001 - 26 Dec 2023
Cited by 1 | Viewed by 2096
Abstract
This review covers the diagnostic potential of urinary biomarkers, shedding light on their linkage to cancer progression. Urinary biomarkers offer non-invasive avenues for detecting cancers, potentially bypassing the invasiveness of biopsies. The investigation focuses primarily on breast and prostate cancers due to their [...] Read more.
This review covers the diagnostic potential of urinary biomarkers, shedding light on their linkage to cancer progression. Urinary biomarkers offer non-invasive avenues for detecting cancers, potentially bypassing the invasiveness of biopsies. The investigation focuses primarily on breast and prostate cancers due to their prevalence among women and men, respectively. The intricate interplay of urinary proteins is explored, revealing a landscape where proteins exhibit context-dependent behaviors. The review highlights the potential impact of physical activity on urinary proteins, suggesting its influence on tumorigenic behaviors. Exercise-conditioned urine may emerge as a potential diagnostic biomarker source. Furthermore, treatment effects, notably after lumpectomy and prostatectomy, induce shifts in the urinary proteome, indicating therapeutic impacts rather than activating oncogenic signaling. The review suggests further investigations into the double-sided, context-dependent nature of urinary proteins, the potential role of post-translational modifications (PTM), and the integration of non-protein markers like mRNA and metabolites. It also discusses a linkage of urinary proteomes with secretomes from induced tumor-suppressing cells (iTSCs). Despite challenges like cancer heterogeneity and sample variability due to age, diet, and comorbidities, harnessing urinary proteins and proteoforms may hold promise for advancing our understanding of cancer progressions, as well as the diagnostic and therapeutic role of urinary proteins. Full article
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