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1. A. Maroli. THE HUMAN-RESTRICTED DUPLICATED FORM OF THE ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR, CHRFAM7A: TRANSCRIPTIONAL REGULATION, ROLE IN INFLAMMATION AND POTENTIAL PHARMACOLOGICAL IMPLICATIONS.

Degree: 2017, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/489077 

The α7 nicotine acetylcholine receptor (α7nAChR, CHRNA7) is a homo-pentameric ligand-gated ion channel widely expressed in the Central Nervous System (CNS). Recent evidence has demonstrated its expression also in non-neuronal tissues, including monocytes and macrophages, where it mediates the Cholinergic Anti-Inflammatory Pathway, a neuronal reflex providing the central control of systemic inflammation. Recently, the human-restricted duplicated gene of the α7nAChR, called CHRFAM7A (α7dup) has been discovered. It is the product of the partial duplication and fusion of exon 5-10 of CHRNA7 gene with the novel exons D, C, B and A belonging to the FAM7A gene, of unknown function. The CHRFAM7A gene is expressed in human immune cells and in the CNS and is translated into two proteins, of 45 kDa and 36 kDa, which are the result of alternative splicing. The α7dup protein assembles with the α7 conventional subunits and exerts a dominant negative regulation on the α7nAChR function. The importance of the α7dup protein in the human inflammatory process has been confirmed by the demonstration of its responsiveness to pro-inflammatory stimuli: indeed, the Lipopolysaccharide (LPS) treatment of THP-1 monocytic cells and of human primary monocytes and macrophages down-regulates CHRFAM7A transcript and protein through a transcriptional mechanism reliant on the NF-κB transcription factor. Moreover, unpublished data demonstrated that LPS has the opposite effect on the α7 transcript in monocytes and macrophages, leading to CHRNA7 up-regulation. In this study, we have investigated the transcriptional mechanisms leading to CHRFAM7A expression in the THP-1 monocytic cells and in neuroblastoma SH-SY5Y cells and we demonstrate that the CHRFAM7A gene is endowed with several complex transcriptional mechanisms leading to fine expression modulation, including the presence of alternative and tissue-specific Transcription Start Site (TSS), alternative splicing mechanism, tissue-specific transcriptional elements and intronic silencer elements. Moreover, we demonstrated that the CHRFAM7A down-regulation exerted by LPS involve the chromatin remodeling of CHRFAM7A promoter in THP-1 cells. Increasing evidence has linked CHRNA7 expressional and functional dysregulation to several neurodegenerative disorders, including Alzheimer’s disease. The treatment with the acetylcholinesterase inhibitor Donepezil is effective in temporary ameliorating the cognitive symptoms of AD, by increasing the synaptic levels of ACh and counteracting the cholinergic loss, which is characteristic of AD. However, emerging findings sustained that Donepezil can exert its therapeutic effect also by modulating the immune response and potentiating the Cholinergic Anti-Inflammatory Pathway. So far, the role of CHRFAM7A gene in AD pathogenesis or pharmacological response has not been elucidated. In the present study, we have investigated the expression profile of CHRNA7 and CHRFAM7A genes in human nervous and immune tissues obtained from AD patients, highlighting expressional… Advisors/Committee Members: relatore: G. Pietrini, coordinatore: M. Locati, PIETRINI, GRAZIA, PIETRINI, GRAZIA, LOCATI, MASSIMO.

Subjects/Keywords: CHRFAM7A; CHRNA7; Inflammation; Alzheimer's disease; Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Maroli, A. (2017). THE HUMAN-RESTRICTED DUPLICATED FORM OF THE ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR, CHRFAM7A: TRANSCRIPTIONAL REGULATION, ROLE IN INFLAMMATION AND POTENTIAL PHARMACOLOGICAL IMPLICATIONS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/489077

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Maroli, A.. “THE HUMAN-RESTRICTED DUPLICATED FORM OF THE ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR, CHRFAM7A: TRANSCRIPTIONAL REGULATION, ROLE IN INFLAMMATION AND POTENTIAL PHARMACOLOGICAL IMPLICATIONS.” 2017. Thesis, Università degli Studi di Milano. Accessed January 16, 2021. http://hdl.handle.net/2434/489077.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Maroli, A.. “THE HUMAN-RESTRICTED DUPLICATED FORM OF THE ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR, CHRFAM7A: TRANSCRIPTIONAL REGULATION, ROLE IN INFLAMMATION AND POTENTIAL PHARMACOLOGICAL IMPLICATIONS.” 2017. Web. 16 Jan 2021.

Vancouver:

Maroli A. THE HUMAN-RESTRICTED DUPLICATED FORM OF THE ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR, CHRFAM7A: TRANSCRIPTIONAL REGULATION, ROLE IN INFLAMMATION AND POTENTIAL PHARMACOLOGICAL IMPLICATIONS. [Internet] [Thesis]. Università degli Studi di Milano; 2017. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/2434/489077.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Maroli A. THE HUMAN-RESTRICTED DUPLICATED FORM OF THE ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR, CHRFAM7A: TRANSCRIPTIONAL REGULATION, ROLE IN INFLAMMATION AND POTENTIAL PHARMACOLOGICAL IMPLICATIONS. [Thesis]. Università degli Studi di Milano; 2017. Available from: http://hdl.handle.net/2434/489077

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


University of Houston

2. Kagalwala, Hamza. Sensory Gating Analysis in Individuals with Copy Number Variants of CHRNA7.

Degree: MSin Electrical Engineering, Electrical Engineering, University of Houston

URL: http://hdl.handle.net/10657/2805 

Sensory gating, the brain’s ability to suppress irrelevant stimuli, was studied in 15 subjects with CHRNA7 gene deletions, 16 with gene duplications, and 28 of their siblings. Pairs of brief tones were repeatedly presented and the brain’s responses to the first (S1) and second (S2) tone in each pair were recorded during baseline in all subjects, and after administration of a placebo and actual medication, respectively in the gene abnormality groups. The amplitude, latency and area under the curve were measured for the P50, N100 and P200 component. Siblings had smaller P200 amplitudes for S1 than patients, but no gating differences were observed. The P50 amplitude for S2 was smaller after medication than at baseline, and the corresponding gating ratio approached significance. In conclusion, subjects with CHRNA7 gene abnormalities and their siblings have similar gating ratios, but medication tends to reduce the P50 gating deficit. Advisors/Committee Members: Jansen, Ben H. (advisor), Hiscock, Merrill (committee member), Ogmen, Haluk (committee member), Schaaf, Christian Patrick (committee member).

Subjects/Keywords: EEG; Sensory gating; Sensory neuroscience; CHRNA7

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Kagalwala, H. (n.d.). Sensory Gating Analysis in Individuals with Copy Number Variants of CHRNA7. (Masters Thesis). University of Houston. Retrieved from http://hdl.handle.net/10657/2805

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Chicago Manual of Style (16th Edition):

Kagalwala, Hamza. “Sensory Gating Analysis in Individuals with Copy Number Variants of CHRNA7.” Masters Thesis, University of Houston. Accessed January 16, 2021. http://hdl.handle.net/10657/2805.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

MLA Handbook (7th Edition):

Kagalwala, Hamza. “Sensory Gating Analysis in Individuals with Copy Number Variants of CHRNA7.” Web. 16 Jan 2021.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

Kagalwala H. Sensory Gating Analysis in Individuals with Copy Number Variants of CHRNA7. [Internet] [Masters thesis]. University of Houston; [cited 2021 Jan 16]. Available from: http://hdl.handle.net/10657/2805.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Council of Science Editors:

Kagalwala H. Sensory Gating Analysis in Individuals with Copy Number Variants of CHRNA7. [Masters Thesis]. University of Houston; Available from: http://hdl.handle.net/10657/2805

Note: this citation may be lacking information needed for this citation format:
No year of publication.

3. Bakanidze, George. Potentielle Biomarker der Schizophrenie - 3 Studien zur Genetik.

Degree: 2018, Freie Universität Berlin

URL: http://dx.doi.org/10.17169/refubium-4484 

Die Rolle der Genetik in der Entstehung psychiatrischer Erkrankungen ist seit langem bekannt. Die Komplexität der genetischen Grundlage der meisten psychiatrischen Erkrankungen erschwert jedoch die Forschung. Deswegen hat die Identifikation von so genannten Endophenotypen die genetische Psychiatrieforschung der letzten Jahrzehnte geprägt. Die vorliegende Dissertation stellt eine Zusammenfassung von drei genetischen Studien dar, die möglichen Biomarker verschiedener Domänen der menschlichen Psychophysiologie untersucht haben. Ein Zusammenhang der frühen visuellen Verarbeitung mit dem cholinergem System wurde untersucht. Es wurde ein signifikanter Einfluss von cholinergic receptor nicotinic alpha 7 subunit (CHRNA7) (rs904952) auf frühe visuelle Verarbeitung gefunden (p=0.021). In der zweiten Studie wurde die mögliche Rolle von dystrobrevin binding protein 1 (DTNBP1) in der Regulierung von kognitiven Prozessen untersucht und ein signifikanter Einfluss von DTNBP1 auf Aufmerksamkeit gefunden (p=0.030). In der dritten Studie wurde die Rolle von inetr-alpha-trypsin inhibitor heavy chain 3 (ITIH3) (rs2535629) hinsichtlich der Therapieantwort auf antipsychotische Medikation bei Schizophreniepatienten untersucht. Es zeigte sich ein statistisch signifikanter Einfluss auf die Besserung von Negativsymptomen unter der Behandlung mit Clozapin. Die Ergebnisse dieser Studien zeigen die Bedeutung des cholinergen Systems in der Pathogenese der Schizophrenie und die Rolle von DTNBP1 in der Regulation kognitive Funktionen. Außerdem leisten sie einen Beitrag zu der Erforschung individualisierter Behandlung psychiatrischer Krankheiten. Insgesamt unterstreichen diese Ergebnisse die Komplexität der genetischen Architektur psychiatrischer Störungen und stimulieren weitere Forschung. Advisors/Committee Members: m (gender), N.N. (firstReferee), N.N. (furtherReferee).

Subjects/Keywords: CHRNA7; DTNBP1; ITIH3; schizophrenia; cognitive functions; glutamate; cholinergic; biomarker; visual backward masking; 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit

…Study 1, five SNPs of CHRNA7 (rs3826029, rs2337506, rs982574, rs904952, rs2337980)… …2000; Stephens et al., 2009) and once again showed the association of CHRNA7 with a… …acetylcholine receptor subunit gene (CHRNA7) with schizophrenia. Schizophrenia research 109… …Association of the Nicotinic Receptor alpha7 Subunit Gene (CHRNA7) with Schizophrenia and… 

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Bakanidze, G. (2018). Potentielle Biomarker der Schizophrenie - 3 Studien zur Genetik. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-4484

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Bakanidze, George. “Potentielle Biomarker der Schizophrenie - 3 Studien zur Genetik.” 2018. Thesis, Freie Universität Berlin. Accessed January 16, 2021. http://dx.doi.org/10.17169/refubium-4484.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Bakanidze, George. “Potentielle Biomarker der Schizophrenie - 3 Studien zur Genetik.” 2018. Web. 16 Jan 2021.

Vancouver:

Bakanidze G. Potentielle Biomarker der Schizophrenie - 3 Studien zur Genetik. [Internet] [Thesis]. Freie Universität Berlin; 2018. [cited 2021 Jan 16]. Available from: http://dx.doi.org/10.17169/refubium-4484.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bakanidze G. Potentielle Biomarker der Schizophrenie - 3 Studien zur Genetik. [Thesis]. Freie Universität Berlin; 2018. Available from: http://dx.doi.org/10.17169/refubium-4484

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.