Special Issue "Lysosomal Storage Disorders"

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

Deadline for manuscript submissions: 15 July 2020.

Special Issue Editor

Special Issue Information

Dear Colleagues,

Lysosomal storage disorders (LSDs) are rare monogenic diseases characterized by aberrant lysosomes with storage material. These diseases often manifest as neurodegeneration and mental retardation, and are associated with a reduced life span. Most LSDs result from the deficiency of a single enzyme, whereas others are caused by mutations in non-enzymatic proteins. The molecular mechanisms and cellular pathology of these diseases have been subject to intensive research for decades, but no therapy options for many of these diseases are available. However, ever more preclinical studies on novel therapies such as gene therapy, chaperone therapy, and enzyme replacement therapy have been emerging in the past few years.

The purpose of this Special Issue is to summarize our current understanding about the disease pathogenesis and molecular mechanisms of LSDs, and to explore therapeutic strategies that could be used in LSDs. We also welcome manuscripts addressing the involvement of various cellular pathways such as autophagy, neuroinflammation, endosomal dysfunction, and signaling in the pathogenesis of LSDs. Novel concepts such as the common features of LSDs and other neurodegenerative diseases such as Alzheimer’s or Parkinson’s are also a subject of this Special Issue. We encourage the submission of review articles and original research papers of any length. Our aim is to provide a comprehensive update on LSDs, their pathomechanisms, and therapy options.

Prof. Dr. Ritva Tikkanen
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. Cells is an international peer-reviewed open access monthly 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 2000 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

  • lysosomes
  • lysosomal storage disorders
  • neurodegeneration
  • enzyme replacement
  • gene therapy
  • substrate reduction
  • pharmacological chaperones
  • autophagy
  • endosomal dysfunction

Published Papers (3 papers)

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

Research

Jump to: Review

Open AccessArticle
An Autophagy Modifier Screen Identifies Small Molecules Capable of Reducing Autophagosome Accumulation in a Model of CLN3-Mediated Neurodegeneration
Cells 2019, 8(12), 1531; https://doi.org/10.3390/cells8121531 - 27 Nov 2019
Cited by 1
Abstract
Alterations in the autophagosomal–lysosomal pathway are a major pathophysiological feature of CLN3 disease, which is the most common form of childhood-onset neurodegeneration. Accumulating autofluorescent lysosomal storage material in CLN3 disease, consisting of dolichols, lipids, biometals, and a protein that normally resides in the [...] Read more.
Alterations in the autophagosomal–lysosomal pathway are a major pathophysiological feature of CLN3 disease, which is the most common form of childhood-onset neurodegeneration. Accumulating autofluorescent lysosomal storage material in CLN3 disease, consisting of dolichols, lipids, biometals, and a protein that normally resides in the mitochondria, subunit c of the mitochondrial ATPase, provides evidence that autophagosomal–lysosomal turnover of cellular components is disrupted upon loss of CLN3 protein function. Using a murine neuronal cell model of the disease, which accurately mimics the major gene defect and the hallmark features of CLN3 disease, we conducted an unbiased search for modifiers of autophagy, extending previous work by further optimizing a GFP-LC3 based assay and performing a high-content screen on a library of ~2000 bioactive compounds. Here we corroborate our earlier screening results and identify expanded, independent sets of autophagy modifiers that increase or decrease the accumulation of autophagosomes in the CLN3 disease cells, highlighting several pathways of interest, including the regulation of calcium signaling, microtubule dynamics, and the mevalonate pathway. Follow-up analysis on fluspirilene, nicardipine, and verapamil, in particular, confirmed activity in reducing GFP-LC3 vesicle burden, while also demonstrating activity in normalizing lysosomal positioning and, for verapamil, in promoting storage material clearance in CLN3 disease neuronal cells. This study demonstrates the potential for cell-based screening studies to identify candidate molecules and pathways for further work to understand CLN3 disease pathogenesis and in drug development efforts. Full article
(This article belongs to the Special Issue Lysosomal Storage Disorders)
Show Figures

Figure 1

Review

Jump to: Research

Open AccessReview
The Role of Hematopoietic Cell Transplant in the Glycoprotein Diseases
Cells 2020, 9(6), 1411; https://doi.org/10.3390/cells9061411 - 05 Jun 2020
Abstract
The glycoprotein disorders are a group of lysosomal storage diseases (α-mannosidosis, aspartylglucosaminuria, β-mannosidosis, fucosidosis, galactosialidosis, sialidosis, mucolipidosis II, mucolipidosis III, and Schindler Disease) characterized by specific lysosomal enzyme defects and resultant buildup of undegraded glycoprotein substrates. This buildup causes a multitude of abnormalities [...] Read more.
The glycoprotein disorders are a group of lysosomal storage diseases (α-mannosidosis, aspartylglucosaminuria, β-mannosidosis, fucosidosis, galactosialidosis, sialidosis, mucolipidosis II, mucolipidosis III, and Schindler Disease) characterized by specific lysosomal enzyme defects and resultant buildup of undegraded glycoprotein substrates. This buildup causes a multitude of abnormalities in patients including skeletal dysplasia, inflammation, ocular abnormalities, liver and spleen enlargement, myoclonus, ataxia, psychomotor delay, and mild to severe neurodegeneration. Pharmacological treatment options exist through enzyme replacement therapy (ERT) for a few, but therapies for this group of disorders is largely lacking. Hematopoietic cell transplant (HCT) has been explored as a potential therapeutic option for many of these disorders, as HCT introduces functional enzyme-producing cells into the bone marrow and blood along with the engraftment of healthy donor cells in the central nervous system (presumably as brain macrophages or a type of microglial cell). The outcome of HCT varies widely by disease type. We report our institutional experience with HCT as well as a review of the literature to better understand HCT and outcomes for the glycoprotein disorders. Full article
(This article belongs to the Special Issue Lysosomal Storage Disorders)
Open AccessReview
Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy
Cells 2020, 9(4), 979; https://doi.org/10.3390/cells9040979 - 15 Apr 2020
Cited by 1
Abstract
Cathepsins (CTSs) are ubiquitously expressed proteases normally found in the endolysosomal compartment where they mediate protein degradation and turnover. However, CTSs are also found in the cytoplasm, nucleus, and extracellular matrix where they actively participate in cell signaling, protein processing, and trafficking through [...] Read more.
Cathepsins (CTSs) are ubiquitously expressed proteases normally found in the endolysosomal compartment where they mediate protein degradation and turnover. However, CTSs are also found in the cytoplasm, nucleus, and extracellular matrix where they actively participate in cell signaling, protein processing, and trafficking through the plasma and nuclear membranes and between intracellular organelles. Dysregulation in CTS expression and/or activity disrupts cellular homeostasis, thus contributing to many human diseases, including inflammatory and cardiovascular diseases, neurodegenerative disorders, diabetes, obesity, cancer, kidney dysfunction, and others. This review aimed to highlight the involvement of CTSs in inherited lysosomal storage disorders, with a primary focus to the emerging evidence on the role of CTSs in the pathophysiology of Mucopolysaccharidoses (MPSs). These latter diseases are characterized by severe neurological, skeletal and cardiovascular phenotypes, and no effective cure exists to date. The advance in the knowledge of the molecular mechanisms underlying the activity of CTSs in MPSs may open a new challenge for the development of novel therapeutic approaches for the cure of such intractable diseases. Full article
(This article belongs to the Special Issue Lysosomal Storage Disorders)
Show Figures

Figure 1

Back to TopTop