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Cells
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Cellular, Molecular and Multi-Omics Approaches for the Investigation of Human...
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Cellular, Molecular and Multi-Omics Approaches for the Investigation of Human Neurodevelopmental Disorders

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cells of the Nervous System".

Deadline for manuscript submissions: 30 April 2024 | Viewed by 2948

Special Issue Editors

Dr. Roberto Hirochi Herai

E-Mail Website
Guest Editor
Experimental Multiuser Laboratory, Graduate Program in Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil
Interests: bioinformatics; high throughput sequencing technologies; neurological disorders; human molecular genetics; molecular biology; systems biology; computational biology; multi-omics data integration; stem cell models for mental disorders.
Dr. Janaína Sena De Souza

E-Mail Website
Guest Editor
Department of Pediatrics, University of California San Diego, San Diego, CA, USA
Interests: neurodegenerative and neurodevelopmental disorders; regenerative medicine; stem cells; brain organoids; neurons; astrocytes; neural progenitor cells; thyroid hormone; endocrine disruptors; complement system

Special Issue Information

Dear Colleagues,

Neurodevelopmental disorders (ND) involve a wide range of health conditions affecting the normal function of the brain and are characterized by early onset of clinical manifestations affecting mood, thinking and behavior, as well as impairments in cognition and motor function. Epidemiological studies indicate a high incidence of ND, affecting millions of people worldwide. To uncover the cellular and molecular mechanisms determining the pathological phenotypes found in ND, recent discoveries have demonstrated several cellular, molecular and genetic phenotypes that are exclusive to ND, with several of them used as biomarkers for their diagnosis as well as for novel drug targets for future therapeutic applications.

Dr. Roberto Hirochi Herai
Dr. Janaína Sena De Souza
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. 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

  • neurodevelopmental disorders
  • multi-omics technologies
  • molecular pathways
  • stem cell for disease modeling
  • regenerative medicine

Published Papers (2 papers)

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Research

14 pages, 3625 KiB  
Article
Proteome Analysis of Thyroid Hormone Transporter Mct8/Oatp1c1-Deficient Mice Reveals Novel Dysregulated Target Molecules Involved in Locomotor Function
by Devon Siemes, Pieter Vancamp, Boyka Markova, Philippa Spangenberg, Olga Shevchuk, Bente Siebels, Hartmut Schlüter, Steffen Mayerl, Heike Heuer and Daniel Robert Engel
Cells 2023, 12(20), 2487; https://doi.org/10.3390/cells12202487 - 19 Oct 2023
Cited by 2 | Viewed by 1318
Abstract
Thyroid hormone (TH) transporter MCT8 deficiency causes severe locomotor disabilities likely due to insufficient TH transport across brain barriers and, consequently, compromised neural TH action. As an established animal model for this disease, Mct8/Oatp1c1 double knockout (DKO) mice exhibit strong central TH deprivation, [...] Read more.
Thyroid hormone (TH) transporter MCT8 deficiency causes severe locomotor disabilities likely due to insufficient TH transport across brain barriers and, consequently, compromised neural TH action. As an established animal model for this disease, Mct8/Oatp1c1 double knockout (DKO) mice exhibit strong central TH deprivation, locomotor impairments and similar histo-morphological features as seen in MCT8 patients. The pathways that cause these neuro-motor symptoms are poorly understood. In this paper, we performed proteome analysis of brain sections comprising cortical and striatal areas of 21-day-old WT and DKO mice. We detected over 2900 proteins by liquid chromatography mass spectrometry, 67 of which were significantly different between the genotypes. The comparison of the proteomic and published RNA-sequencing data showed a significant overlap between alterations in both datasets. In line with previous observations, DKO animals exhibited decreased myelin-associated protein expression and altered protein levels of well-established neuronal TH-regulated targets. As one intriguing new candidate, we unraveled and confirmed the reduced protein and mRNA expression of Pde10a, a striatal enzyme critically involved in dopamine receptor signaling, in DKO mice. As altered PDE10A activities are linked to dystonia, reduced basal ganglia PDE10A expression may represent a key pathogenic pathway underlying human MCT8 deficiency. Full article
(This article belongs to the Special Issue Cellular, Molecular and Multi-Omics Approaches for the Investigation of Human Neurodevelopmental Disorders)
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16 pages, 7203 KiB  
Article
Clinical Cases and the Molecular Profiling of a Novel Childhood Encephalopathy-Causing GNAO1 Mutation P170R
by Yonika A. Larasati, Gonzalo P. Solis, Alexey Koval, Silja T. Griffiths, Ragnhild Berentsen, Ingvild Aukrust, Gaetan Lesca, Nicolas Chatron, Dorothée Ville, Christian M. Korff and Vladimir L. Katanaev
Cells 2023, 12(20), 2469; https://doi.org/10.3390/cells12202469 - 17 Oct 2023
Cited by 1 | Viewed by 1085
Abstract
De novo mutations in GNAO1, the gene encoding the major neuronal G protein Gαo, cause a spectrum of pediatric encephalopathies with seizures, motor dysfunction, and developmental delay. Of the >80 distinct missense pathogenic variants, many appear to uniformly destabilize the guanine nucleotide [...] Read more.
De novo mutations in GNAO1, the gene encoding the major neuronal G protein Gαo, cause a spectrum of pediatric encephalopathies with seizures, motor dysfunction, and developmental delay. Of the >80 distinct missense pathogenic variants, many appear to uniformly destabilize the guanine nucleotide handling of the mutant protein, speeding up GTP uptake and deactivating GTP hydrolysis. Zinc supplementation emerges as a promising treatment option for this disease, as Zn2+ ions reactivate the GTP hydrolysis on the mutant Gαo and restore cellular interactions for some of the mutants studied earlier. The molecular etiology of GNAO1 encephalopathies needs further elucidation as a prerequisite for the development of efficient therapeutic approaches. In this work, we combine clinical and medical genetics analysis of a novel GNAO1 mutation with an in-depth molecular dissection of the resultant protein variant. We identify two unrelated patients from Norway and France with a previously unknown mutation in GNAO1, c.509C>G that results in the production of the Pro170Arg mutant Gαo, leading to severe developmental and epileptic encephalopathy. Molecular investigations of Pro170Arg identify this mutant as a unique representative of the pathogenic variants. Its 100-fold-accelerated GTP uptake is not accompanied by a loss in GTP hydrolysis; Zn2+ ions induce a previously unseen effect on the mutant, forcing it to lose the bound GTP. Our work combining clinical and molecular analyses discovers a novel, biochemically distinct pathogenic missense variant of GNAO1 laying the ground for personalized treatment development. Full article
(This article belongs to the Special Issue Cellular, Molecular and Multi-Omics Approaches for the Investigation of Human Neurodevelopmental Disorders)
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