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Current Insights into the Neuronal Calcium Sensor DREAM and Related KChIP Proteins

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (30 December 2023) | Viewed by 2859

Special Issue Editors

Prof. Dr. Jose R. Naranjo

E-Mail Website
Guest Editor
Centro Nacional de Biotecnología–Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, Spain
Interests: calcium and protein homeostasis
Dr. Jaroslava Miksovska

E-Mail Website
Guest Editor
Department of Chemistry and Biochemistry, Florida International University, MM Campus, Miami, FL 33199, USA
Interests: hemeproteins; calcium binding proteins; protein structure; ligand binding

Special Issue Information

Dear Colleagues,

The neuronal calcium sensor DREAM, also known as calsenilin or KChIP3, is a multifunctional protein widely expressed in the CNS and peripheral organs. DREAM activities are determined by specific protein–DNA and protein–protein interactions in specific subcellular compartments in a wide variety of cellular types, both in adulthood and during development. Importantly, the binding of divalent ions, lipids and small molecules to DREAM changes its conformation and impacts it ability to interact with other macromolecules. Thus, the activity of DREAM could be modulated both physiologically and pharmacologically.

In this Special Issue, we would like to recapitulate recent advances in all aspects concerning DREAM and related KChIP1, 2 and 4 proteins. This includes similarities and specificities in their regulation and their functions in health and disease, as well as new developments in the binding molecules able to alter their activity.

Prof. Dr. Jose R. Naranjo
Dr. Jaroslava Miksovska
Guest Editors

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • calcium homeostasis
  • protein–protein interactions
  • EF-hands
  • neurodegeneration
  • fibrosis
  • DREAM ligands

Published Papers (2 papers)

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Research

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16 pages, 3868 KiB  
Article
Repaglinide Induces ATF6 Processing and Neuroprotection in Transgenic SOD1G93A Mice
by Rafael Gonzalo-Gobernado, Laura Moreno-Martínez, Paz González, Xose Manuel Dopazo, Ana Cristina Calvo, Isabel Pidal-Ladrón de Guevara, Elisa Seisdedos, Rodrigo Díaz-Muñoz, Britt Mellström, Rosario Osta and José Ramón Naranjo
Int. J. Mol. Sci. 2023, 24(21), 15783; https://doi.org/10.3390/ijms242115783 - 30 Oct 2023
Viewed by 952
Abstract
The interaction of the activating transcription factor 6 (ATF6), a key effector of the unfolded protein response (UPR) in the endoplasmic reticulum, with the neuronal calcium sensor Downstream Regulatory Element Antagonist Modulator (DREAM) is a potential therapeutic target in neurodegeneration. Modulation of the [...] Read more.
The interaction of the activating transcription factor 6 (ATF6), a key effector of the unfolded protein response (UPR) in the endoplasmic reticulum, with the neuronal calcium sensor Downstream Regulatory Element Antagonist Modulator (DREAM) is a potential therapeutic target in neurodegeneration. Modulation of the ATF6–DREAM interaction with repaglinide (RP) induced neuroprotection in a model of Huntington’s disease. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no cure, characterized by the progressive loss of motoneurons resulting in muscle denervation, atrophy, paralysis, and death. The aim of this work was to investigate the potential therapeutic significance of DREAM as a target for intervention in ALS. We found that the expression of the DREAM protein was reduced in the spinal cord of SOD1G93A mice compared to wild-type littermates. RP treatment improved motor strength and reduced the expression of the ALS progression marker collagen type XIXα1 (Col19α1 mRNA) in the quadriceps muscle in SOD1G93A mice. Moreover, treated SOD1G93A mice showed reduced motoneuron loss and glial activation and increased ATF6 processing in the spinal cord. These results indicate that the modulation of the DREAM–ATF6 interaction ameliorates ALS symptoms in SOD1G93A mice. Full article
(This article belongs to the Special Issue Current Insights into the Neuronal Calcium Sensor DREAM and Related KChIP Proteins)
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Review

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13 pages, 3306 KiB  
Review
Emerging Role of DREAM in Healthy Brain and Neurological Diseases
by Pasquale Molinaro, Luca Sanguigno, Antonella Casamassa, Valeria Valsecchi, Rossana Sirabella, Giuseppe Pignataro, Lucio Annunziato and Luigi Formisano
Int. J. Mol. Sci. 2023, 24(11), 9177; https://doi.org/10.3390/ijms24119177 - 24 May 2023
Cited by 1 | Viewed by 1586
Abstract
The downstream regulatory element antagonist modulator (DREAM) is a multifunctional Ca2+-sensitive protein exerting a dual mechanism of action to regulate several Ca2+-dependent processes. Upon sumoylation, DREAM enters in nucleus where it downregulates the expression of several genes provided with [...] Read more.
The downstream regulatory element antagonist modulator (DREAM) is a multifunctional Ca2+-sensitive protein exerting a dual mechanism of action to regulate several Ca2+-dependent processes. Upon sumoylation, DREAM enters in nucleus where it downregulates the expression of several genes provided with a consensus sequence named dream regulatory element (DRE). On the other hand, DREAM could also directly modulate the activity or the localization of several cytosolic and plasma membrane proteins. In this review, we summarize recent advances in the knowledge of DREAM dysregulation and DREAM-dependent epigenetic remodeling as a central mechanism in the progression of several diseases affecting central nervous system, including stroke, Alzheimer’s and Huntington’s diseases, amyotrophic lateral sclerosis, and neuropathic pain. Interestingly, DREAM seems to exert a common detrimental role in these diseases by inhibiting the transcription of several neuroprotective genes, including the sodium/calcium exchanger isoform 3 (NCX3), brain-derived neurotrophic factor (BDNF), pro-dynorphin, and c-fos. These findings lead to the concept that DREAM might represent a pharmacological target to ameliorate symptoms and reduce neurodegenerative processes in several pathological conditions affecting central nervous system. Full article
(This article belongs to the Special Issue Current Insights into the Neuronal Calcium Sensor DREAM and Related KChIP Proteins)
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