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Cells
Special Issues
Cellular and Molecular Basis of Alkaptonuria
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Cellular and Molecular Basis of Alkaptonuria

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: 31 March 2025 | Viewed by 4443

Special Issue Editors

Prof. Dr. Annalisa Santucci

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Guest Editor
Dipartimento de Biotecnologie, Chimica e FarmaciaUniversità de Sienavia Aldo Moro, 253100 Siena, Italy
Interests: post-genomics; omics
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Ottavia Spiga

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Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro 2, 53100 Siena, Italy
Interests: bioinformatics; structural biology; big data analysis
Prof. Dr. Daniela Braconi

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Department Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy
Interests: Clinical biomarkers
Special Issues, Collections and Topics in MDPI journals
Dr. Giulia Bernardini

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Guest Editor
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy
Interests: novel therapeutics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Alkaptonuria (AKU) is an ultra-rare disease associated with the low activity of homogentisate 1,2-dioxygenase (HGD), which catabolizes homogentisic acid (HGA), due to HGD mutations, but with no clear genotype–phenotype correlation. In AKU, HGA is not metabolized, and it accumulates as a pigment in connective tissues, causing oxidative stress-mediated tissue and organ degeneration followed by disability and pain in patients. Such is the need for further research into this disease that the first therapeutic intervention based on nitisinone has been only recently implemented.

Multidisciplinary approaches combining genetic analysis, in silico studies, molecular modelling, cell, tissue and animal models, cell biology, biochemistry and post-genomics, histopathology, bioinformatics, AI and analytical chemistry complemented by clinical data have provided novel relevant insights into AKU’s molecular mechanisms, showing how AKU is a very complex disease with a range of AKU-associated comorbidities.

The Special Issue aims to comprehensively integrate the broad range of all the multidisciplinary data so far collected and to present novel relevant data on AKU’s pathophysiology, alongside the biomarkers discovered for prognosis and diagnosis, therapeutic targets and clinical monitoring, thus providing tools for physicians and researchers and creating a pathway towards a precision medicine approach.

AKU may be seen as a model disease sharing features with other inflammatory and chronic diseases. Therefore, contributions from scientists conducting research into cellular, molecular and clinical data that can provide useful novel clues for investigations into AKU will also be welcome.

Prof. Dr. Annalisa Santucci
Prof. Dr. Ottavia Spiga
Prof. Dr. Daniela Braconi
Dr. Giulia Bernardini
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. Cells is an international peer-reviewed open access semimonthly 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

  • Alkaptonuria
  • AKU
  • pathophysiology
  • post-genomics
  • histopathology
  • bioinformatics

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Published Papers (2 papers)

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Research

8 pages, 266 KiB  
Communication
Evaluation of Homogentisic Acid, a Prospective Antibacterial Agent Highlighted by the Suitability of Nitisinone in Alkaptonuria 2 (SONIA 2) Clinical Trial
by Nicola Ooi, Ian R. Cooper, Brendan Norman, James A. Gallagher, Nick Sireau, George Bou-Gharios, Lakshminarayan R. Ranganath and Victoria J. Savage
Cells 2023, 12(13), 1683; https://doi.org/10.3390/cells12131683 - 21 Jun 2023
Viewed by 1829
Abstract
Despite urgent warnings about the spread of multidrug-resistant bacteria, the antibiotic development pipeline has remained sparsely populated. Naturally occurring antibacterial compounds may provide novel chemical starting points for antibiotic development programs and should be actively sought out. Evaluation of homogentisic acid (HGA), an [...] Read more.
Despite urgent warnings about the spread of multidrug-resistant bacteria, the antibiotic development pipeline has remained sparsely populated. Naturally occurring antibacterial compounds may provide novel chemical starting points for antibiotic development programs and should be actively sought out. Evaluation of homogentisic acid (HGA), an intermediate in the tyrosine degradation pathway, showed that the compound had innate activity against Gram-positive and Gram-negative bacteria, which was lost following conversion into the degradation product benzoquinone acetic acid (BQA). Anti-staphylococcal activity of HGA can be attributed to effects on bacterial membranes. Despite an absence of haemolytic activity, the compound was cytotoxic to human HepG2 cells. We conclude that the antibacterial activity and in vitro safety profile of HGA render it more suitable for use as a topical agent or for inclusion in a small-molecule medicinal chemistry program. Full article
(This article belongs to the Special Issue Cellular and Molecular Basis of Alkaptonuria)
14 pages, 1674 KiB  
Article
Effects of Nitisinone on Oxidative and Inflammatory Markers in Alkaptonuria: Results from SONIA1 and SONIA2 Studies
by Daniela Braconi, Michela Geminiani, Eftychia Eirini Psarelli, Daniela Giustarini, Barbara Marzocchi, Ranieri Rossi, Giulia Bernardini, Ottavia Spiga, James A. Gallagher, Kim-Hanh Le Quan Sang, Jean-Baptiste Arnoux, Richard Imrich, Mohammed S. Al-Sbou, Matthew Gornall, Richard Jackson, Lakshminarayan R. Ranganath and Annalisa Santucci
Cells 2022, 11(22), 3668; https://doi.org/10.3390/cells11223668 - 18 Nov 2022
Cited by 2 | Viewed by 1864
Abstract
Nitisinone (NTBC) was recently approved to treat alkaptonuria (AKU), but there is no information on its impact on oxidative stress and inflammation, which are observed in AKU. Therefore, serum samples collected during the clinical studies SONIA1 (40 AKU patients) and SONIA2 (138 AKU [...] Read more.
Nitisinone (NTBC) was recently approved to treat alkaptonuria (AKU), but there is no information on its impact on oxidative stress and inflammation, which are observed in AKU. Therefore, serum samples collected during the clinical studies SONIA1 (40 AKU patients) and SONIA2 (138 AKU patients) were tested for Serum Amyloid A (SAA), CRP and IL-8 by ELISA; Advanced Oxidation Protein Products (AOPP) by spectrophotometry; and protein carbonyls by Western blot. Our results show that NTBC had no significant effects on the tested markers except for a slight but statistically significant effect for NTBC, but not for the combination of time and NTBC, on SAA levels in SONIA2 patients. Notably, the majority of SONIA2 patients presented with SAA > 10 mg/L, and 30 patients in the control group (43.5%) and 40 patients (58.0%) in the NTBC-treated group showed persistently elevated SAA > 10 mg/L at each visit during SONIA2. Higher serum SAA correlated with lower quality of life and higher morbidity. Despite no quantitative differences in AOPP, the preliminary analysis of protein carbonyls highlighted patterns that deserve further investigation. Overall, our results suggest that NTBC cannot control the sub-clinical inflammation due to increased SAA observed in AKU, which is also a risk factor for developing secondary amyloidosis. Full article
(This article belongs to the Special Issue Cellular and Molecular Basis of Alkaptonuria)
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