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Cells
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Nicotinic Receptors in Health and Disease
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Nicotinic Receptors in Health and Disease

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 7173

Special Issue Editor

Prof. Dr. Ada Maria Tata

E-Mail Website
Guest Editor
Department of Biology and Biotechnologies Charles Darwin, Research Center of Neurobiology Daniel Bovet, Sapienza University of Rome, 00185 Rome, Italy
Interests: acetylcholine; acetylcholine receptors; development; inflammation; cancer; nervous system pathologies

Special Issue Information

Dear Colleagues,

Although nicotinic receptors have been identified in muscle, they are largely expressed in the central and peripheral nervous system, both in neurons and glial cells. In the central nervous system, nAChRs are located in the pre-, post-, and extra-synaptic regions. Moreover, considering their wide expression in other tissues, such as lung epithelium, macrophages, and microglia, their potential involvement in different physiological functions is emerging. In the present issue, we will cover the roles played by different nicotinic receptors in several tissues in normal and pathological conditions. In fact, several studies indicate the involvement of nicotinic receptors in several pathologies, such as autism, intellectual disabilities, schizophrenia, Alzheimer’s, as well as autoimmune disorders and cancer. Although significant progress has been achieved in receptor expression, distribution and physiological functions, molecular mechanisms, and effector proteins activated downstream, nicotinic receptor activation remain to be further investigated. A discussion around nicotinic ligands will also be considered. 

Prof. Dr. Ada Maria Tata
Guest Editor

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

  • nicotinic receptors
  • nicotinic ligands
  • copy number variations
  • development
  • inflammation
  • neuroinflammation
  • cancer
  • immunological function
  • neurodegenerative diseases
  • autoimmune disorders
  • nicotinic receptor signaling

Published Papers (3 papers)

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Research

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16 pages, 2006 KiB  
Article
α7 Nicotinic Acetylcholine Receptors May Improve Schwann Cell Regenerating Potential via Metabotropic Signaling Pathways
by Elisabetta Botticelli, Claudia Guerriero, Sergio Fucile, Maria Egle De Stefano, Carlo Matera, Clelia Dallanoce, Marco De Amici and Ada Maria Tata
Cells 2023, 12(11), 1494; https://doi.org/10.3390/cells12111494 - 28 May 2023
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Abstract
Background: Schwann cells (SCs) are glial cells involved in peripheral axon myelination. SCs also play a strategic role after peripheral nerve injury, regulating local inflammation and axon regeneration. Our previous studies demonstrated the presence of cholinergic receptors in SCs. In particular, the α7 [...] Read more.
Background: Schwann cells (SCs) are glial cells involved in peripheral axon myelination. SCs also play a strategic role after peripheral nerve injury, regulating local inflammation and axon regeneration. Our previous studies demonstrated the presence of cholinergic receptors in SCs. In particular, the α7 nicotinic acetylcholine receptors (nAChRs) are expressed in SCs after peripheral axotomy, suggesting their involvement in the regulation of SC-regenerating properties. To clarify the role that α7 nAChRs may play after peripheral axon damage, in this study we investigated the signal transduction pathways triggered by receptor activation and the effects produced by their activation. Methods: Both ionotropic and metabotropic cholinergic signaling were analyzed by calcium imaging and Western blot analysis, respectively, following α7 nAChR activation. In addition, the expression of c-Jun and α7 nAChRs was evaluated by immunocytochemistry and Western blot analysis. Finally, the cell migration was studied by a wound healing assay. Results: Activation of α7 nAChRs, activated by the selective partial agonist ICH3, did not induce calcium mobilization but positively modulated the PI3K/AKT/mTORC1 axis. Activation of the mTORC1 complex was also supported by the up-regulated expression of its specific p-p70 S6KThr389 target. Moreover, up-regulation of p-AMPKThr172, a negative regulator of myelination, was also observed concomitantly to an increased nuclear accumulation of the transcription factor c-Jun. Cell migration and morphology analyses proved that α7 nAChR activation also promotes SC migration. Conclusions: Our data demonstrate that α7 nAChRs, expressed by SCs only after peripheral axon damage and/or in an inflammatory microenvironment, contribute to improve the SCs regenerating properties. Indeed, α7 nAChR stimulation leads to an upregulation of c-Jun expression and promotes Schwann cell migration by non-canonical pathways involving the mTORC1 activity. Full article
(This article belongs to the Special Issue Nicotinic Receptors in Health and Disease)
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Review

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21 pages, 2062 KiB  
Review
Nicotinic Acetylcholine Receptor Dysfunction in Addiction and in Some Neurodegenerative and Neuropsychiatric Diseases
by Ana Sofía Vallés and Francisco J. Barrantes
Cells 2023, 12(16), 2051; https://doi.org/10.3390/cells12162051 - 11 Aug 2023
Cited by 6 | Viewed by 3149
Abstract
The cholinergic system plays an essential role in brain development, physiology, and pathophysiology. Herein, we review how specific alterations in this system, through genetic mutations or abnormal receptor function, can lead to aberrant neural circuitry that triggers disease. The review focuses on the [...] Read more.
The cholinergic system plays an essential role in brain development, physiology, and pathophysiology. Herein, we review how specific alterations in this system, through genetic mutations or abnormal receptor function, can lead to aberrant neural circuitry that triggers disease. The review focuses on the nicotinic acetylcholine receptor (nAChR) and its role in addiction and in neurodegenerative and neuropsychiatric diseases and epilepsy. Cholinergic dysfunction is associated with inflammatory processes mainly through the involvement of α7 nAChRs expressed in brain and in peripheral immune cells. Evidence suggests that these neuroinflammatory processes trigger and aggravate pathological states. We discuss the preclinical evidence demonstrating the therapeutic potential of nAChR ligands in Alzheimer disease, Parkinson disease, schizophrenia spectrum disorders, and in autosomal dominant sleep-related hypermotor epilepsy. PubMed and Google Scholar bibliographic databases were searched with the keywords indicated below. Full article
(This article belongs to the Special Issue Nicotinic Receptors in Health and Disease)
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Other

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43 pages, 1524 KiB  
Systematic Review
A Systematic Review on Drugs Acting as Nicotinic Acetylcholine Receptor Agonists in the Treatment of Dementia
by Alessio Crestini, Elena Carbone, Roberto Rivabene, Antonio Ancidoni, Paolo Rosa, Ada Maria Tata, Elisa Fabrizi, Nicoletta Locuratolo, Nicola Vanacore, Eleonora Lacorte and Paola Piscopo
Cells 2024, 13(3), 237; https://doi.org/10.3390/cells13030237 - 26 Jan 2024
Cited by 1 | Viewed by 2134
Abstract
Acetylcholine signaling is attenuated in early Alzheimer’s disease (AD) and other dementias. A significant reduction in the expression of nicotinic acetylcholine receptors (nAChRs) in the brain of AD patients has also been reported in several molecular biological and in situ labeling studies. The [...] Read more.
Acetylcholine signaling is attenuated in early Alzheimer’s disease (AD) and other dementias. A significant reduction in the expression of nicotinic acetylcholine receptors (nAChRs) in the brain of AD patients has also been reported in several molecular biological and in situ labeling studies. The modulation of the functional deficit of the cholinergic system as a pharmacological target could therefore have a clinical benefit, which is not to be neglected. This systematic review was conducted to identify clinical trials, which evaluated the safety and efficacy of nicotinic acetylcholine receptor agonists using Clinicaltrial (CT) and EudraCT databases. Structured searches identified 39 trials, which used 15 different drugs designed to increase the function of the nAChRs. Most of the identified clinical trials were phase II trials, with some of them classified as ongoing for several years. The systematic screening of the literature led to the selection of 14 studies out of the 8261 bibliographic records retrieved. Six trials reported detailed data on adverse events associated with the intervention, while twelve trials reported data on efficacy measures, such as attention, behavior and cognition. Overall, smost of the physical side effects of cholinergic agonists were reported to be well tolerated. Some trials also reported improvements in attention. However, the efficacy of these drugs in other cognitive and behavioral outcomes remains highly controversial. Full article
(This article belongs to the Special Issue Nicotinic Receptors in Health and Disease)
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