Nanostructural Modulation of G-Quadruplex DNA in Neurodegeneration: Orotate Interaction Revealed Through Experimental and Computational Approaches (961 views)
Journal Of Neurochemistry, 2025 Jan 20; 169: e16296-N/D.
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Paper type: Research Journal Article
Impact factor: 4.2, 5-year impact factor: 0
Url: https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.16296
Keywords: Amyotrophic Lateral Sclerosis (als), Food Drugs, Frontotemporal Dementia (ftd), G-Quadruplex Dna, Orotate, Orotic Acid
Affiliations:
*** IBB - CNR ***
Andrea Patrizia Falanga 1 | Ilaria Piccialli 2 | Francesca Greco1 | Stefano D'Errico1 | Maria Grazia Nolli1 |Nicola Borbone1,3 | Giorgia Oliviero3,4 | Giovanni N. Roviello51 Department of Pharmacy, University of Naples Federico II, Naples, Italy | 2 Division of Pharmacology, Department of Neuroscience, Reproductiveand Dentistry Sciences, School of Medicine, University of Naples Federico II, Naples, Italy | 3 ISBE-IT, University of Naples Federico II, Naples,Italy | 4 Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy | 5 Institute of Biostructures andBioimaging, Italian National Council for Research (IBB- CNR), Naples, Italy
References:
Journal Of Neurochemistry, 2025 Jan 20; 169: e16296-N/D.
Export to BibTeX Export to EndNote
Paper type: Research Journal Article
Impact factor: 4.2, 5-year impact factor: 0
Url: https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.16296
Keywords: Amyotrophic Lateral Sclerosis (als), Food Drugs, Frontotemporal Dementia (ftd), G-Quadruplex Dna, Orotate, Orotic Acid
Affiliations:
*** IBB - CNR ***
Andrea Patrizia Falanga 1 | Ilaria Piccialli 2 | Francesca Greco1 | Stefano D'Errico1 | Maria Grazia Nolli1 |Nicola Borbone1,3 | Giorgia Oliviero3,4 | Giovanni N. Roviello51 Department of Pharmacy, University of Naples Federico II, Naples, Italy | 2 Division of Pharmacology, Department of Neuroscience, Reproductiveand Dentistry Sciences, School of Medicine, University of Naples Federico II, Naples, Italy | 3 ISBE-IT, University of Naples Federico II, Naples,Italy | 4 Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy | 5 Institute of Biostructures andBioimaging, Italian National Council for Research (IBB- CNR), Naples, Italy
References:
Nanostructural Modulation of G-Quadruplex DNA in Neurodegeneration: Orotate Interaction Revealed Through Experimental and Computational Approaches
The natural compound orotic acid and its anionic form, orotate, play a pivotal role in various biological processes, serving as essential intermediates in pyrimidine de novo synthesis, with demonstrated connections to dietary, supplement, and neurodrug applications. A novel perspective on biomolecular aggregation at the nanoscale, particularly pertinent to neurodegeneration, challenges the established paradigm positing that peptide (amyloid beta) and protein (tau) aggregation mainly govern the molecular events underlying prevalent neuropathologies. Emerging biological evidence indicates a notable role for G-quadruplex (G4) DNA aggregation in neurodegenerative processes affecting neuronal cells, particularly in the presence of extended (G4C2)n repeats in nuclear DNA sequences. Our study concerns d[(GGGGCC)3GGGG], a G4-forming DNA model featuring G4C2 repeats that is in correlation with neurodegeneration. Through different investigations utilizing spectroscopic techniques (CD, UV, and thermal denaturations), PAGE electrophoresis, and molecular docking, the study explores the influence of orotate on the aggregation of this neurodegeneration-associated DNA. A computational approach was employed to construct an in silico model of the DNA aggregate, which involved the docking of multiple G4 units and subsequent integration of the ligand into both the DNA monomer and its in silico aggregated model. The convergence of computational analyses and empirical data collectively supports the hypothesis that orotate possesses the capability to modulate the aggregation of neurodegeneration-related DNA. Notably, the findings suggest the potential utility of orotate as a neurodrug, especially for the therapy of amyotrophic lateral sclerosis (ALS) and Frontotemporal Dementia (FTD), with its current status as a dietary supplement indicating minimal safety concerns. Additionally, orotate demonstrated a slight increase in mitochondrial dehydrogenase activity as assessed by the MTT assay, which is beneficial for a neurodrug as it suggests a potential role in enhancing mitochondrial function and supporting neuronal health.
The natural compound orotic acid and its anionic form, orotate, play a pivotal role in various biological processes, serving as essential intermediates in pyrimidine de novo synthesis, with demonstrated connections to dietary, supplement, and neurodrug applications. A novel perspective on biomolecular aggregation at the nanoscale, particularly pertinent to neurodegeneration, challenges the established paradigm positing that peptide (amyloid beta) and protein (tau) aggregation mainly govern the molecular events underlying prevalent neuropathologies. Emerging biological evidence indicates a notable role for G-quadruplex (G4) DNA aggregation in neurodegenerative processes affecting neuronal cells, particularly in the presence of extended (G4C2)n repeats in nuclear DNA sequences. Our study concerns d[(GGGGCC)3GGGG], a G4-forming DNA model featuring G4C2 repeats that is in correlation with neurodegeneration. Through different investigations utilizing spectroscopic techniques (CD, UV, and thermal denaturations), PAGE electrophoresis, and molecular docking, the study explores the influence of orotate on the aggregation of this neurodegeneration-associated DNA. A computational approach was employed to construct an in silico model of the DNA aggregate, which involved the docking of multiple G4 units and subsequent integration of the ligand into both the DNA monomer and its in silico aggregated model. The convergence of computational analyses and empirical data collectively supports the hypothesis that orotate possesses the capability to modulate the aggregation of neurodegeneration-related DNA. Notably, the findings suggest the potential utility of orotate as a neurodrug, especially for the therapy of amyotrophic lateral sclerosis (ALS) and Frontotemporal Dementia (FTD), with its current status as a dietary supplement indicating minimal safety concerns. Additionally, orotate demonstrated a slight increase in mitochondrial dehydrogenase activity as assessed by the MTT assay, which is beneficial for a neurodrug as it suggests a potential role in enhancing mitochondrial function and supporting neuronal health.
Nanostructural Modulation of G-Quadruplex DNA in Neurodegeneration: Orotate Interaction Revealed Through Experimental and Computational Approaches
Nanostructural Modulation of G-Quadruplex DNA in Neurodegeneration: Orotate Interaction Revealed Through Experimental and Computational Approaches
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Ewert E, Marcinkowski D, Pospieszna-markiewicz I, Palumbo R, Hnatejko Z, Kubicki M, Gorczyński A, Wieczorek-szweda E, Patroniak V, Roviello GN, Fik-jaskółka M
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Impact Factor: 8.5
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Simonyan H, Palumbo R, Vicidomini C, Scognamiglio PL, Petrosyan S, Sahakyan L, Melikyan G, Saghyan A, Roviello GN
* Binding of G-quadruplex DNA and serum albumins by synthetic non-proteinogenic amino acids: Implications for c-Myc-related anticancer activity and drug delivery (1124 views) (PDF 92 views)
Molecular Therapeutics Nucleic Acids, 2025 Apr 2025; 36: 102478-102478.
Impact Factor: 6.5
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Autiero I, Roviello GN
* Interaction of Laurusides 1 and 2 with the 3C-like Protease (M(pro)) from Wild-Type and Omicron Variant of SARS-CoV-2: A Molecular Dynamics Study (1486 views)
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Impact Factor: 0
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Autiero I, Roviello GN
* Interaction of Laurusides 1 and 2 with the 3C-like Protease (Mpro) from Wild-Type and Omicron Variant of SARS-CoV-2: A Molecular Dynamics Study (969 views)
International Journal Of Molecular Sciences, 2023 Mar; 25: 5511-5511.
Impact Factor: 5.6
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Ricci A, Roviello GN
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Life, 2023 Feb; 13: 402-417.
Impact Factor: 3.2
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Marzano M, Falanga AP, Marasco D, Borbone N, D , #errico S, Piccialli G, Roviello GN, Oliviero G
* Evaluation of an Analogue of the Marine ε-PLL Peptide as a Ligand of G-quadruplex DNA Structures (1388 views) (PDF 182 views)
Mar Drugs (ISSN: 1660-3397linking), 2020 Jan 11; 18(1): 49-60.
Impact Factor: 4.073
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Platella C, Guida S, Bonmassar L, Aquino A, Bonmassar E, Ravagnan G, Montesarchio D, Roviello GN, Musumeci D, Fuggetta MP
* Antitumour activity of resveratrol on human melanoma cells: a possible mechanism related to its interaction with malignant cell telomerase (1766 views)
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Impact Factor: 4.28
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Scognamiglio PL, Di Natale C, Leone M, Poletto M, Vitagliano L, Tell G, Marasco D
* G-quadruplex DNA recognition by nucleophosmin: new insights from protein dissection (1845 views)
Bba-Gen Subjects (ISSN: 0005-2728, 0006-3002print, 1570-9639print), 2014 Jun; 1840(6): 2050-2059.
Impact Factor: 5.353
View Export to BibTeX Export to EndNote
* La(3+) and Dy(3+) hexaaza macrocycles revisited: Enhanced stabilization of G-quadruplex DNA - spectroscopic and in silico studies (63 views)
Int J Biol Macromol, 2025 Oct 17; 330(Pt4): 148269-148281.
Impact Factor: 8.5
View Export to BibTeX Export to EndNote
Simonyan H, Palumbo R, Vicidomini C, Scognamiglio PL, Petrosyan S, Sahakyan L, Melikyan G, Saghyan A, Roviello GN
* Binding of G-quadruplex DNA and serum albumins by synthetic non-proteinogenic amino acids: Implications for c-Myc-related anticancer activity and drug delivery (1124 views) (PDF 92 views)
Molecular Therapeutics Nucleic Acids, 2025 Apr 2025; 36: 102478-102478.
Impact Factor: 6.5
View Export to BibTeX Export to EndNote
Autiero I, Roviello GN
* Interaction of Laurusides 1 and 2 with the 3C-like Protease (M(pro)) from Wild-Type and Omicron Variant of SARS-CoV-2: A Molecular Dynamics Study (1486 views)
Int J Mol Sci (ISSN: 1422-0067linking), 2023 Mar 14; 24 (6 ): N/D-N/D.
Impact Factor: 0
View Export to BibTeX Export to EndNote
Autiero I, Roviello GN
* Interaction of Laurusides 1 and 2 with the 3C-like Protease (Mpro) from Wild-Type and Omicron Variant of SARS-CoV-2: A Molecular Dynamics Study (969 views)
International Journal Of Molecular Sciences, 2023 Mar; 25: 5511-5511.
Impact Factor: 5.6
View Export to BibTeX Export to EndNote
Ricci A, Roviello GN
Exploring the Protective Effect of Food Drugs against Viral Diseases: Interaction of Functional Food Ingredients and SARS-CoV-2, Influenza Virus, and HSV (1688 views)
Life, 2023 Feb; 13: 402-417.
Impact Factor: 3.2
View Export to BibTeX Export to EndNote
Marzano M, Falanga AP, Marasco D, Borbone N, D , #errico S, Piccialli G, Roviello GN, Oliviero G
* Evaluation of an Analogue of the Marine ε-PLL Peptide as a Ligand of G-quadruplex DNA Structures (1388 views) (PDF 182 views)
Mar Drugs (ISSN: 1660-3397linking), 2020 Jan 11; 18(1): 49-60.
Impact Factor: 4.073
View Export to BibTeX Export to EndNote
Platella C, Guida S, Bonmassar L, Aquino A, Bonmassar E, Ravagnan G, Montesarchio D, Roviello GN, Musumeci D, Fuggetta MP
* Antitumour activity of resveratrol on human melanoma cells: a possible mechanism related to its interaction with malignant cell telomerase (1766 views)
Bba-Gen Subjects (ISSN: 0005-2728, 0006-3002print, 1570-9639print), 2017 Aug 02; 1861(11PtA): 2843-2851.
Impact Factor: 4.28
View Export to BibTeX Export to EndNote
Scognamiglio PL, Di Natale C, Leone M, Poletto M, Vitagliano L, Tell G, Marasco D
* G-quadruplex DNA recognition by nucleophosmin: new insights from protein dissection (1845 views)
Bba-Gen Subjects (ISSN: 0005-2728, 0006-3002print, 1570-9639print), 2014 Jun; 1840(6): 2050-2059.
Impact Factor: 5.353
View Export to BibTeX Export to EndNote
8 Records (8 excluding Abstracts).
Total impact factor: 37.506 (37.506 excluding Abstracts).
Total 5 year impact factor: 24.194 (24.194 excluding Abstracts).
Total impact factor: 37.506 (37.506 excluding Abstracts).
Total 5 year impact factor: 24.194 (24.194 excluding Abstracts).
961 views. Last view on Sunday 25 January 2026, 10:21:51
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