Cellular and Molecular Mechanisms of Lysosomal Storage Disorders

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

Deadline for manuscript submissions: 31 March 2024 | Viewed by 1921

Special Issue Editor

Institute of Biochemistry, Medical Faculty, Justus-Liebig University of Giessen, Friedrichstrasse 24, D-35392 Giessen, Germany
Interests: lysosomal storage disorders; vesicular trafficking; endosomal sorting; lysosome biogenesis; mitochondrial diseases; autoimmune disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lysosomal storage disorders (LSDs) are rare, monogenic diseases that are characterized by aberrant lysosomes with storage material. These diseases often manifest as neurodegeneration and are associated with a reduced life span. Many of the LSDs result from a 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 only few therapy options for these diseases are available. However, ever more preclinical studies on novel therapies such as gene therapy, chaperone therapy and enzyme replacement therapy are emerging in the last 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 pathways 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 subjects of interest for this Special Issue. We encourage the submission of comprehensive review articles and original research papers. Our aim is to provide a comprehensive update on LSDs, their pathomechanisms and therapy options.

Prof. Dr. Ritva Tikkanen
Guest Editor

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Keywords

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

Published Papers (1 paper)

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Research

21 pages, 4505 KiB  
Article
Rapamycin Alleviates Protein Aggregates, Reduces Neuroinflammation, and Rescues Demyelination in Globoid Cell Leukodystrophy
by Dar-Shong Lin, Yu-Wen Huang, Tsung-Han Lee, Lung Chang, Zon-Darr Huang, Tsu-Yen Wu, Tuan-Jen Wang and Che-Sheng Ho
Cells 2023, 12(7), 993; https://doi.org/10.3390/cells12070993 - 24 Mar 2023
Cited by 3 | Viewed by 1465
Abstract
We have shown in vivo and in vitro previously that psychosine causes dysfunction of autophagy and the ubiquitin-proteasome system underlying the pathogenesis of globoid cell leukodystrophy (GLD), a devastating lysosomal storage disease complicated by global demyelination. Here, we investigated the therapeutic efficacy of [...] Read more.
We have shown in vivo and in vitro previously that psychosine causes dysfunction of autophagy and the ubiquitin-proteasome system underlying the pathogenesis of globoid cell leukodystrophy (GLD), a devastating lysosomal storage disease complicated by global demyelination. Here, we investigated the therapeutic efficacy of the mTOR inhibitor rapamycin in twitcher mice, a murine model of infantile GLD, in biochemical, histochemical, and clinical aspects. Administration of rapamycin to twitcher mice inhibited mTOR signaling in the brains, and significantly reduced the accumulation of insoluble ubiquitinated protein and the formation of ubiquitin aggregates. The astrocytes and microglia reactivity were attenuated in that reactive astrocytes, ameboid microglia, and globoid cells were reduced in the brains of rapamycin-treated twitcher mice. Furthermore, rapamycin improved the cortical myelination, neurite density, and rescued the network complexity in the cortex of twitcher mice. The therapeutic action of rapamycin on the pathology of the twitcher mice’s brains prolonged the longevity of treated twitcher mice. Overall, these findings validate the therapeutic efficacy of rapamycin and highlight enhancing degradation of aggregates as a therapeutic strategy to modulate neuroinflammation, demyelination, and disease progression of GLD and other leukodystrophies associated with intracellular aggregates. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Lysosomal Storage Disorders)
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