Journal Browser

Journal Browser

Special Issue "New Molecular Insights into Neurocutaneous Syndromes"

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 April 2021).

Special Issue Editor

Dr. Yo Niida
E-Mail Website
Guest Editor
Kanazawa Medical University, Kahoku District, Japan
Interests: new technologies and methods for molecular diagnosis; discovery of disease-severity-determining molecular factors; analysis of molecular pathway dysfunctions and cross-talking abnormalities associated with gene mutations; quest for possibilities of new molecular targeted drugs

Special Issue Information

Dear Colleagues,

Neurocutaneous syndrome is a category of genetic disease characterized by both skin and brain lesions with tumor formation, which comprises neurofibromatosis type 1 (NF1), tuberous sclerosis complex (TSC), Sturge–Weber syndrome (SWS), and various other disorders. In recent years, causative genes of these syndromes have been identified, and these molecules have been revealed to commonly regulate RAS/MAPK and PI3K/mTOR pathways, which are also shared with cancer. This has led to the emergence of a new concept based on which neurocutaneous syndromes have a common molecular basis as a framework, and clinical application of molecular targeted drugs such as mTOR inhibitors has been done. Genetic diagnosis of these syndromes is still difficult because mutation patterns are diverse, including deep intronic mutations, and a certain population of patients have mosaic mutations. SWS (GNAQ) and some rare RAS mutation syndromes are caused by specific gain-of-function mutations as somatic mosaicism. Syndromes caused by haploinsufficiency due to loss-of-function mutations such as NF1 and TSC are basically no genotype–phenotype correlations. However, the severity of individual patient varies even in a single family for some unknown reason. In this Special Issue, we will focus on new molecular insight of neurocutaneous syndromes, welcoming all those studies on more sophisticated genetic diagnosis, discovery of severity-determining factors, analysis of molecular pathway dysfunctions and cross-talking abnormalities associated with gene mutations, and quest for possibilities of new molecular targeted drugs.

Dr. Yo Niida
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 papers will be 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.


  • Neurocutaneous syndromes
  • Neurofibromatosis type 1
  • Tuberous sclerosis complex
  • Sturge–Weber syndrome
  • Molecular diagnosis
  • Mosaic mutation
  • Deep intronic mutation
  • Molecular basis of risk factors for disease severity
  • RAS/MAPK pathway
  • PI3K/mTOR pathway
  • Dysregulation of signal transduction pathway caused by gene mutations
  • Molecular targeted therapy

Published Papers (1 paper)

Order results
Result details
Select all
Export citation of selected articles as:


Open AccessReview
Spontaneous and Engineered Large Animal Models of Neurofibromatosis Type 1
Int. J. Mol. Sci. 2021, 22(4), 1954; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041954 - 16 Feb 2021
Viewed by 643
Animal models are crucial to understanding human disease biology and developing new therapies. By far the most common animal used to investigate prevailing questions about human disease is the mouse. Mouse models are powerful tools for research as their small size, limited lifespan, [...] Read more.
Animal models are crucial to understanding human disease biology and developing new therapies. By far the most common animal used to investigate prevailing questions about human disease is the mouse. Mouse models are powerful tools for research as their small size, limited lifespan, and defined genetic background allow researchers to easily manipulate their genome and maintain large numbers of animals in general laboratory spaces. However, it is precisely these attributes that make them so different from humans and explains, in part, why these models do not accurately predict drug responses in human patients. This is particularly true of the neurofibromatoses (NFs), a group of genetic diseases that predispose individuals to tumors of the nervous system, the most common of which is Neurofibromatosis type 1 (NF1). Despite years of research, there are still many unanswered questions and few effective treatments for NF1. Genetically engineered mice have drastically improved our understanding of many aspects of NF1, but they do not exemplify the overall complexity of the disease and some findings do not translate well to humans due to differences in body size and physiology. Moreover, NF1 mouse models are heavily reliant on the Cre-Lox system, which does not accurately reflect the molecular mechanism of spontaneous loss of heterozygosity that accompanies human tumor development. Spontaneous and genetically engineered large animal models may provide a valuable supplement to rodent studies for NF1. Naturally occurring comparative models of disease are an attractive prospect because they occur on heterogeneous genetic backgrounds and are due to spontaneous rather than engineered mutations. The use of animals with naturally occurring disease has been effective for studying osteosarcoma, lymphoma, and diabetes. Spontaneous NF-like symptoms including neurofibromas and malignant peripheral nerve sheath tumors (MPNST) have been documented in several large animal species and share biological and clinical similarities with human NF1. These animals could provide additional insight into the complex biology of NF1 and potentially provide a platform for pre-clinical trials. Additionally, genetically engineered porcine models of NF1 have recently been developed and display a variety of clinical features similar to those seen in NF1 patients. Their large size and relatively long lifespan allow for longitudinal imaging studies and evaluation of innovative surgical techniques using human equipment. Greater genetic, anatomic, and physiologic similarities to humans enable the engineering of precise disease alleles found in human patients and make them ideal for preclinical pharmacokinetic and pharmacodynamic studies of small molecule, cellular, and gene therapies prior to clinical trials in patients. Comparative genomic studies between humans and animals with naturally occurring disease, as well as preclinical studies in large animal disease models, may help identify new targets for therapeutic intervention and expedite the translation of new therapies. In this review, we discuss new genetically engineered large animal models of NF1 and cases of spontaneous NF-like manifestations in large animals, with a special emphasis on how these comparative models could act as a crucial translational intermediary between specialized murine models and NF1 patients. Full article
(This article belongs to the Special Issue New Molecular Insights into Neurocutaneous Syndromes)
Show Figures

Figure 1

Back to TopTop