Perspectives for Applying G-Quadruplex Structures in Neurobiology and Neuropharmacology

The most common form of DNA is a right-handed helix or the B-form DNA. DNA can also adopt a variety of alternative conformations, non-B-form DNA secondary structures, including the DNA G-quadruplex (DNA-G4). Furthermore, besides stem-loops that yield A-form double-stranded RNA, non-canonical RNA G-quadruplex (RNA-G4) secondary structures are also observed. Recent bioinformatics analysis of the whole-genome and transcriptome obtained using G-quadruplex–specific antibodies and ligands, revealed genomic positions of G-quadruplexes. In addition, accumulating evidence pointed to the existence of these structures under physiologically- and pathologically-relevant conditions, with functional roles in vivo. In this review, we focused on DNA-G4 and RNA-G4, which may have important roles in neuronal function, and reveal mechanisms underlying neurological disorders related to synaptic dysfunction. In addition, we mention the potential of G-quadruplexes as therapeutic targets for neurological diseases.

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Pif1 is essential for efficient replisome progression through lagging strand G-quadruplex DNA secondary structures

Nucleic Acids Research ◽

10.1093/nar/gky1065 ◽

2018 ◽

Vol 46 (22) ◽

pp. 11847-11857 ◽

Cited By ~ 23

Author(s):

Danielle Dahan ◽

Ioannis Tsirkas ◽

Daniel Dovrat ◽

Melanie A Sparks ◽

Saurabh P Singh ◽

...

Keyword(s):

Secondary Structures ◽

Quadruplex Dna ◽

G Quadruplex ◽

Dna Secondary Structures ◽

Lagging Strand

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Light-Induced Formation of G-Quadruplex DNA Secondary Structures

ChemBioChem ◽

10.1002/cbic.200500198 ◽

2005 ◽

Vol 6 (11) ◽

pp. 1966-1970 ◽

Cited By ~ 57

Author(s):

Günter Mayer ◽

Lenz Kröck ◽

Vera Mikat ◽

Marianne Engeser ◽

Alexander Heckel

Keyword(s):

Secondary Structures ◽

Quadruplex Dna ◽

G Quadruplex ◽

Dna Secondary Structures

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Covalently Functionalized DNA Duplexes and Quadruplexes as Hybrid Catalysts in an Enantioselective Friedel–Crafts Reaction

Molecules ◽

10.3390/molecules25143121 ◽

2020 ◽

Vol 25 (14) ◽

pp. 3121

Author(s):

Surjendu Dey ◽

Andres Jäschke

Keyword(s):

Secondary Structures ◽

Catalytic Performance ◽

Dna Duplexes ◽

Quadruplex Dna ◽

Hybrid Catalysts ◽

Modified Dna ◽

G Quadruplex ◽

Dna Secondary Structures ◽

Dna Strand

The precise site-specific positioning of metal–ligand complexes on various DNA structures through covalent linkages has gained importance in the development of hybrid catalysts for aqueous-phase homogeneous catalysis. Covalently modified double-stranded and G-quadruplex DNA-based hybrid catalysts have been investigated separately. To understand the role of different DNA secondary structures in enantioselective Friedel–Crafts alkylation, a well-known G-quadruplex-forming sequence was covalently modified at different positions. The catalytic performance of this modified DNA strand was studied in the presence and absence of a complementary DNA sequence, resulting in the formation of two different secondary structures, namely duplex and G-quadruplex. Indeed, the secondary structures had a tremendous effect on both the yield and stereoselectivity of the catalyzed reaction. In addition, the position of the modification, the topology of the DNA, the nature of the ligand, and the length of the linker between ligand and DNA were found to modulate the catalytic performance of the hybrid catalysts. Using the optimal linker length, the quadruplexes formed the (−)-enantiomer with up to 65% ee, while the duplex yielded the (+)-enantiomer with up to 62% ee. This study unveils a new and simple way to control the stereochemical outcome of a Friedel–Crafts reaction.

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Replication of G Quadruplex DNA

Genes ◽

10.3390/genes10020095 ◽

2019 ◽

Vol 10 (2) ◽

pp. 95 ◽

Cited By ~ 34

Author(s):

Leticia Koch Lerner ◽

Julian E. Sale

Keyword(s):

Dna Replication ◽

Dna Sequences ◽

Secondary Structures ◽

Dna Unwinding ◽

Chromosomal Dna ◽

Quadruplex Dna ◽

Epigenetic Instability ◽

G Quadruplex ◽

Dna Secondary Structures ◽

Dna Template

A cursory look at any textbook image of DNA replication might suggest that the complex machine that is the replisome runs smoothly along the chromosomal DNA. However, many DNA sequences can adopt non-B form secondary structures and these have the potential to impede progression of the replisome. A picture is emerging in which the maintenance of processive DNA replication requires the action of a significant number of additional proteins beyond the core replisome to resolve secondary structures in the DNA template. By ensuring that DNA synthesis remains closely coupled to DNA unwinding by the replicative helicase, these factors prevent impediments to the replisome from causing genetic and epigenetic instability. This review considers the circumstances in which DNA forms secondary structures, the potential responses of the eukaryotic replisome to these impediments in the light of recent advances in our understanding of its structure and operation and the mechanisms cells deploy to remove secondary structure from the DNA. To illustrate the principles involved, we focus on one of the best understood DNA secondary structures, G quadruplexes (G4s), and on the helicases that promote their resolution.

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Cover Picture: Light-Induced Formation of G-Quadruplex DNA Secondary Structures (ChemBioChem 11/2005)

ChemBioChem ◽

10.1002/cbic.200590036 ◽

2005 ◽

Vol 6 (11) ◽

pp. 1913-1913

Author(s):

Günter Mayer ◽

Lenz Kröck ◽

Vera Mikat ◽

Marianne Engeser ◽

Alexander Heckel

Keyword(s):

Secondary Structures ◽

Quadruplex Dna ◽

G Quadruplex ◽

Dna Secondary Structures

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Erratum: Corrigendum: Structural revisions of small molecules reported to cross-link G-quadruplex DNA in vivo reveal a repetitive assignment error in the literature

Scientific Reports ◽

10.1038/srep40471 ◽

2017 ◽

Vol 7 (1) ◽

Author(s):

Paul E. Reyes-Gutiérrez ◽

Tomáš Kapal ◽

Blanka Klepetářová ◽

David Šaman ◽

Radek Pohl ◽

...

Keyword(s):

Small Molecules ◽

Cross Link ◽

Quadruplex Dna ◽

G Quadruplex ◽

Assignment Error

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Molecular Imaging in Traditional Chinese Medicine Therapy for Neurological Diseases

BioMed Research International ◽

10.1155/2013/608430 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 15

Author(s):

Zefeng Wang ◽

Haitong Wan ◽

Jinhui Li ◽

Hong Zhang ◽

Mei Tian

Keyword(s):

Chinese Medicine ◽

Molecular Imaging ◽

Traditional Chinese Medicine ◽

Neurological Disorders ◽

Neurological Diseases ◽

Chinese Herb ◽

Public Health Care ◽

Therapeutic Effects ◽

Cord Injury

With the speeding tendency of aging society, human neurological disorders have posed an ever increasing threat to public health care. Human neurological diseases include ischemic brain injury, Alzheimer’s disease, Parkinson’s disease, and spinal cord injury, which are induced by impairment or specific degeneration of different types of neurons in central nervous system. Currently, there are no more effective treatments against these diseases. Traditional Chinese medicine (TCM) is focused on, which can provide new strategies for the therapy in neurological disorders. TCM, including Chinese herb medicine, acupuncture, and other nonmedication therapies, has its unique therapies in treating neurological diseases. In order to improve the treatment of these disorders by optimizing strategies using TCM and evaluate the therapeutic effects, we have summarized molecular imaging, a new promising technology, to assess noninvasively disease specific in cellular and molecular levels of living models in vivo, that was applied in TCM therapy for neurological diseases. In this review, we mainly focus on applying diverse molecular imaging methodologies in different TCM therapies and monitoring neurological disease, and unveiling the mysteries of TCM.

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G-quadruplex DNA drives genomic instability and represents a targetable molecular abnormality in ATRX-deficient malignant glioma

10.1101/347542 ◽

2018 ◽

Author(s):

Yuxiang Wang ◽

Jie Yang ◽

Wei Wu ◽

Rachna Shah ◽

Carla Danussi ◽

...

Keyword(s):

Dna Damage ◽

Malignant Glioma ◽

Model Systems ◽

Copy Number Alterations ◽

Molecular Alteration ◽

Quadruplex Dna ◽

G4 Dna ◽

G Quadruplex

AbstractMutational inactivation of ATRX (α-thalassemia mental retardation X-linked) represents a defining molecular alteration in large subsets of malignant glioma. Yet the pathogenic consequences of ATRX deficiency remain unclear, as do tractable mechanisms for its therapeutic targeting. Here we report that ATRX loss in isogenic glioma model systems induces replication stress and DNA damage by way of G-quadruplex (G4) DNA secondary structure. Moreover, these effects are associated with the acquisition of disease-relevant copy number alterations over time. We then demonstrate, both in vitro and in vivo, that ATRX deficiency selectively enhances DNA damage and cell death following chemical G4 stabilization. Finally, we show that G4 stabilization synergizes with other DNA-damaging therapies, including ionizing radiation, in the ATRX-deficient context. Our findings reveal novel pathogenic mechanisms driven by ATRX deficiency in glioma, while also pointing to tangible strategies for drug development.

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Locus Coeruleus Magnetic Resonance Imaging in Neurological Diseases

Current Neurology and Neuroscience Reports ◽

10.1007/s11910-020-01087-7 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Alessandro Galgani ◽

Francesco Lombardo ◽

Daniele Della Latta ◽

Nicola Martini ◽

Ubaldo Bonuccelli ◽

...

Keyword(s):

Locus Coeruleus ◽

Neurological Disorders ◽

Potential Role ◽

Neurological Diseases ◽

Mri Findings ◽

Promising Tool ◽

Experimental Tool ◽

Early Biomarker ◽

The Brain

Abstract Purpose of Review Locus coeruleus (LC) is the main noradrenergic nucleus of the brain, and its degeneration is considered to be key in the pathogenesis of neurodegenerative diseases. In the last 15 years,MRI has been used to assess LC in vivo, both in healthy subjects and in patients suffering from neurological disorders. In this review, we summarize the main findings of LC-MRI studies, interpreting them in light of preclinical and histopathological data, and discussing its potential role as diagnostic and experimental tool. Recent findings LC-MRI findings were largely in agreement with neuropathological evidences; LC signal showed to be not significantly affected during normal aging and to correlate with cognitive performances. On the contrary, a marked reduction of LC signal was observed in patients suffering from neurodegenerative disorders, with specific features. Summary LC-MRI is a promising tool, which may be used in the future to explore LC pathophysiology as well as an early biomarker for degenerative diseases.

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