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Special Issue "Advances in Knowledge in Niemann-Pick Disease Type C: Facts and Perspectives"

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: 25 February 2020.

Special Issue Editors

Prof. MERCÈ PALLAS LLIBERIA
E-Mail Website
Guest Editor
Universitat de Barcelona, Barcelona, Spain
Interests: Ageing; Neurodegeneration; Alzheimer's disease; Neuropharmacology; Oxidative stress; Mitochondria; Proteostasis; Epigenetics
Dr. Daniel Ortuño-Sahagún
E-Mail
Guest Editor
Instituto de Investigación en Ciencias Biomédicas (IICB), Centro Universitario de Ciencias de las Salud (CUCS), Universidad de Guadalajara, Sierra Mojada No. 950, Col. Independencia, Guadalajara, 44340, Jalisco, Mexico
Interests: Gene Expresion Profiles; Neurodegenerative Diseases; Aging; Neuromodulation; Immunomodulation; Neuroimmune molecular basis; Epigenetics

Special Issue Information

Dear Colleagues,

Niemann–Pick disease Type C (NPC) is an autosomal recessive neurodegenerative disease with a progressive and fatal outcome. Due to its low incidence, it is classified as rare disease, with no effective treatment so far. Today, the denomination designates disorders characterized by unique abnormalities in intracellular cholesterol transport by endocytic trafficking with sequestration of unesterified cholesterol in late endosomes/lysosomes. However, significant advances that led to the elucidation of this disease occurred after the description of the two underlying genes NPC1 and NPC2, with 95% of cases associated to mutations in NPC1.

The disease is mostly diagnosed during childhood and progresses to life-threatening complications early in life; patients typically display cerebellar ataxia, difficulty speaking and swallowing, with progressive dementia. Histopathological hallmarks for NPC include the endosomal/lysosomal system with aberrant cholesterol and glycosphingolipids accumulation. Those are key symptoms and signs for NPC diagnosis and are also easy to follow both clinically and experimentally. However, we are still far from understanding how the loss of NPC1 function leads to signs and to the development of the disease.

This Special Issue is focused on the breakthroughs on NPC knowledge from a molecular point of view up to the therapeutic approach. Not only is basic research in animal models necessary to dissect the role of the NPC1 gene in physiological and pathological conditions, but also applied clinical research is mandatory in order to reach the cutting edge of scientific advances that will finally benefit patients, and the sooner this happens, the better.

Prof. MERCÈ PALLAS LLIBERIA
Dr. Daniel Ortuño-Sahagún
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 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.

Keywords

  • Niemann–Pick C
  • Rare diseases
  • Lysosomal storage
  • Neurodegeneration
  • Cerebellar degeneration
  • Sphingomyelinase
  • Orphan disease
  • Therapy

Published Papers (2 papers)

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Research

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Open AccessArticle
Structural Determination of Lysosphingomyelin-509 and Discovery of Novel Class Lipids from Patients with Niemann–Pick Disease Type C
Int. J. Mol. Sci. 2019, 20(20), 5018; https://doi.org/10.3390/ijms20205018 - 10 Oct 2019
Abstract
Niemann–Pick disease type C (NPC) is an autosomal recessive disorder caused by the mutation of cholesterol-transporting proteins. In addition, early treatment is important for good prognosis of this disease because of the progressive neurodegeneration. However, the diagnosis of this disease is difficult due [...] Read more.
Niemann–Pick disease type C (NPC) is an autosomal recessive disorder caused by the mutation of cholesterol-transporting proteins. In addition, early treatment is important for good prognosis of this disease because of the progressive neurodegeneration. However, the diagnosis of this disease is difficult due to a variety of clinical spectrum. Lysosphingomyelin-509, which is one of the most useful biomarkers for NPC, was applied for the rapid and easy detection of NPC. The fact that its chemical structure was unknown until recently implicates the unrevealed pathophysiology and molecular mechanisms of NPC. In this study, we aimed to elucidate the structure of lysosphingomyelin-509 by various mass spectrometric techniques. As our identification strategy, we adopted analytical and organic chemistry approaches to the serum of patients with NPC. Chemical derivatization and hydrogen abstraction dissociation–tandem mass spectrometry were used for the determination of function groups and partial structure, respectively. As a result, we revealed the exact structure of lysosphingomyelin-509 as N-acylated and O-phosphocholine adducted serine. Additionally, we found that a group of metabolites with N-acyl groups were increased considerably in the serum/plasma of patients with NPC as compared to that of other groups using targeted lipidomics analysis. Our techniques were useful for the identification of lysosphingomyelin-509. Full article
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Review

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Open AccessReview
Current Challenges in Understanding the Cellular and Molecular Mechanisms in Niemann–Pick Disease Type C1
Int. J. Mol. Sci. 2019, 20(18), 4392; https://doi.org/10.3390/ijms20184392 - 06 Sep 2019
Abstract
Rare diseases are a heterogeneous group of very different clinical syndromes. Their most common causes are defects in the hereditary material, and they can therefore be passed on to descendants. Rare diseases become manifest in almost all organs and often have a systemic [...] Read more.
Rare diseases are a heterogeneous group of very different clinical syndromes. Their most common causes are defects in the hereditary material, and they can therefore be passed on to descendants. Rare diseases become manifest in almost all organs and often have a systemic expressivity, i.e., they affect several organs simultaneously. An effective causal therapy is often not available and can only be developed when the underlying causes of the disease are understood. In this review, we focus on Niemann–Pick disease type C1 (NPC1), which is a rare lipid-storage disorder. Lipids, in particular phospholipids, are a major component of the cell membrane and play important roles in cellular functions, such as extracellular receptor signaling, intracellular second messengers and cellular pressure regulation. An excessive storage of fats, as seen in NPC1, can cause permanent damage to cells and tissues in the brain and peripheral nervous system, but also in other parts of the body. Here, we summarize the impact of NPC1 pathology on several organ systems, as revealed in experimental animal models and humans, and give an overview of current available treatment options. Full article
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