scholarly journals DNA repair enzyme NEIL3 enables a stable neural representation of space by shaping transcription in hippocampal neurons

iScience ◽  
2021 ◽  
pp. 103470
Author(s):  
Nicolas Kunath ◽  
Anna Maria Bugaj ◽  
Pegah Bigonah ◽  
Marion Silvana Fernandez-Berrocal ◽  
Magnar Bjørås ◽  
...  
Keyword(s):  
Dna Repair ◽  
Hippocampal Neurons ◽  
Neural Representation ◽  
Repair Enzyme ◽  
Representation Of Space

scholarly journals DNA Repair Enzyme NEIL3 Enables a Stable Neural Representation of Space by Shaping Transcription in Hippocampal Neurons

2021 ◽  
Author(s):  
Nicolas Kunath ◽  
Anna Maria Bugaj ◽  
Pegah Bigonah ◽  
Marion Silvana Fernandez-Berrocal ◽  
Magnar Bjørås ◽  
...  
Keyword(s):  
Dna Repair ◽  
Hippocampal Neurons ◽  
Neural Representation ◽  
Repair Enzyme ◽  
Representation Of Space

scholarly journals DNA repair enzyme NEIL3 enables a stable neural representation of space by shaping transcription in hippocampal neurons

2021 ◽  
Author(s):  
Nicolas Kunath ◽  
Anna Maria Bugaj ◽  
Pegah Bigonah ◽  
Marion Silvana Fernandez-Berrocal ◽  
Magnar Bjørås ◽  
...  
Keyword(s):  
Dna Repair ◽  
Hippocampal Neurons ◽  
Spatial Information ◽  
Excision Repair ◽  
Place Cells ◽  
Neural Representation ◽  
Brain Functions ◽  
Dna Base Excision Repair ◽  
Representation Of Space ◽  
Base Excision

ABSTRACTDNA repair enzymes are essential for the maintenance of neuronal genome and thereby proper brain functions. NEIL3 is a member of the NEIL family DNA glycosylases initiating oxidative DNA base excision repair. Recent studies show that NEIL3-deficiency leads to impaired spatial performance in mice, decreased adult neurogenesis and altered synaptic composition in the hippocampus. However, it remains elusive how NEIL3 contributes to spatial information coding in hippocampal neurons. Here, we revealed impaired spatial stability in Neil3−/− CA1 place cells, demonstrating a functional interference of NEIL3 with spatial representations. We identified NEIL3-dependent transcriptional changes in response to spatial exploration and defined its regulatory role specifically for NMDA receptor subunits and immediate early genes. Our work demonstrates a non-canonical role of NEIL3 in modulating the functional plasticity of place cells by shaping the neuronal transcriptome, thus sheds light on the molecular determinants enabling a stable neural representation of space.

Long-term efficacy of a new medical device containing Fernblock® and DNA repair enzyme complex in the treatment and prevention of cancerization field in patients with actinic keratosis.

2019 ◽  
Vol 2 (02) ◽  
pp. 80-89
Author(s):  
Blanca De Unamuno Bustos ◽  
Natalia Chaparr´´o Aguilera ◽  
Inmaculada Azorín García ◽  
Anaid Calle Andrino ◽  
Margarita Llavador Ros ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Medical Device ◽  
Actinic Keratosis ◽  
Statistical Significance ◽  
Dna Lesions ◽  
Enzyme Complex ◽  
Repair Enzyme ◽  
P53 Expression ◽  
Cancerization Field

Actinic keratosis (AKs) are part of the cancerization field, a region adjacent to AKs containing subclinical and histologically abnormal epidermal tissue due to Ultraviolet (UV)-induced DNA damage. The photoproducts as consequence of DNA damage induced by UV are mainly cyclobutane pyrimidine dimers (CPDs). Fernblock® demonstrated in previous studies significant reduction of the number of CPDs induced by UV radiation. Photolyases are a specific group of enzymes that remove the major UV-induced DNA lesions by a mechanism called photo-reactivation. A monocentric, prospective, controlled, and double blind interventional study was performed to evaluate the effect of a new medical device (NMD) containing a DNA-repair enzyme complex (photolyases, endonucleases and glycosilases), a combination of UV-filters, and Fernblock® in the treatment of the cancerization field in 30 AK patients after photodynamic therapy. Patients were randomized into two groups: patients receiving a standard sunscreen (SS) andpatients receiving the NMD. Clinical, dermoscopic, reflectance confocal microscopy (RCM) and histological evaluations were performed. An increase of AKs was noted in all groups after three months of PDT without significant differences between them (p=0.476). A significant increase in the number of AKs was observed in SS group after six (p=0.026) and twelve months of PDT (p=0.038); however, this increase did not reach statistical significance in the NMD group. Regarding RCM evaluation, honeycomb pattern assessment after twelve months of PDT showed significant differences in the extension and grade of the atypia in the NMD group compared to SS group (p=0.030 and p=0.026, respectively). Concerning histopathological evaluation, keratinocyte atypia grade improved from baseline to six months after PDT in all the groups, with no statistically significant differences between the groups. Twelve months after PDT, p53 expression was significantly lower in the NMD group compared to SS group (p=0.028). The product was well-tolerated, with no serious adverse events reported. Our results provide evidence of the utility of this NMD in the improvement of the cancerization field and in the prevention of the development of new AKs.  

The Development of Tyrosyl-DNA Phosphodyesterase 1 (TDP1) Inhibitors Based on the Amines Combining Aromatic/Heteroaromatic and Monoterpenoid Moieties

2019 ◽  
Vol 16 (5) ◽  
pp. 597-605 ◽  
Author(s):  
Evgenii Mozhaitsev ◽  
Evgenii Suslov ◽  
Yuliya Demidova ◽  
Dina Korchagina ◽  
Konstantin Volcho ◽  
...  
Keyword(s):  
Dna Repair ◽  
Tumor Cell ◽  
13C Nmr ◽  
Inhibitory Activity ◽  
Secondary Amines ◽  
Repair Enzyme ◽  
1H And 13C Nmr ◽  
Chemical Structures ◽  
Natural Substances ◽  
Micromolar Range

Background: Inhibition of the DNA repair enzyme, tyrosyl-DNA phosphodiesterase 1 (TDP1), may increase the efficacy of cancer drugs that cause damage to tumor cell DNA. Among the known TDP1 inhibitors, there are compounds containing moieties of natural substances, e.g., monoterpenoids. In this work, we synthesized several compounds containing aromatic/ heteroaromatic amines and monoterpenoid groups and assessed their TDP1 inhibition potential. Methods: Structures of all the synthesized compounds were confirmed by 1H and 13C NMR as well as HRMS. The TDP1 inhibitory activity of the amines was determined by real-time fluorescence oligonucleotide biosensor. Results: The synthesized secondary amines had TDP1 inhibitory activity IC50 in the range of 0.79-9.2 µM. The highest activity was found for (–)-myrtenal derivatives containing p-bromoaniline or m-(trifluoromethyl)aniline residue. Conclusion: We synthesized 22 secondary amines; of these, 17 amines are novel chemical structures. Many of the amines inhibit TDP1 activity in the low micromolar range. Therefore, these compounds are promising for further study of their antiproliferative activity in conjunction with DNA damaging drugs.

Neural Representation of Space Using Sinusoidal Arrays

1993 ◽  
Vol 5 (6) ◽  
pp. 869-884 ◽  
Author(s):  
David S. Touretzky ◽  
A. David Redish ◽  
Hank S. Wan
Keyword(s):  
Computer Simulations ◽  
Parietal Cortex ◽  
Spatial Information ◽  
Sine Wave ◽  
Spiking Neurons ◽  
Neural Representation ◽  
Temporal Dimension ◽  
Response Properties ◽  
Representation Of Space

O'Keefe (1991) has proposed that spatial information in rats might be represented as phasors: phase and amplitude of a sine wave encoding angle and distance to a landmark. We describe computer simulations showing that operations on phasors can be efficiently realized by arrays of spiking neurons that recode the temporal dimension of the sine wave spatially. Some cells in motor and parietal cortex exhibit response properties compatible with this proposal.

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