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Cytokines in Lysosomal Storage Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 2813

Special Issue Editor

Special Issue Information

Dear Colleagues,

In many of the lysosomal storage diseases (LSDs), including the Gaucher, Fabry, Tay–Sachs, Sandhoff, Niemann–Pick, Farbar, Krabbe, Metachromatic Leukodystrophy, Wolmen, and Mucopolysaccharidoses diseases, the pathological consequences of the accumulation of certain lipids and complex sugars in tissues include the generation of a massive amount of pro-inflammatory cytokines, including interleukin-1α (IL-1α), interleukin-1β (IL-β), tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ), IL-6, IL-8, IL-10, IL-12, and IL-17. These cytokines are linked to the inflammation and destruction of tissue (e.g., liver, spleen, lung, kidney, bone, and brain tissue) in LSDs. The cost to treat most LSD patients with enzyme replacement or substrate reduction therapy is very expensive: approximately $100,000–300,000 per year. The effects of such therapies are limited as they decrease the accumulation of several types of lipids and complex sugars in tissues but are less effective at preventing the innate and adaptive immune inflammation that leads to organ dysfunction and destruction in LSDs. It is clear that additional therapies are needed to address major disease manifestations. In this Special Issue, we aim to systematically survey recently identified cytokines and their role in the propagation of disease complications in different LSDs. Clinical strategies for targeting cytokines and/or their receptors could help us to slow down and/or stop lipid- and complex-sugar-induced tissue inflammation in different LSDs.

Dr. Manoj K. Pandey
Guest Editor

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Published Papers (1 paper)

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Research

22 pages, 63532 KiB  
Article
Reduced Granule Cell Proliferation and Molecular Dysregulation in the Cerebellum of Lysosomal Acid Phosphatase 2 (ACP2) Mutant Mice
by Xiaodan Jiao, Maryam Rahimi Balaei, Ejlal Abu-El-Rub, Filippo Casoni, Hassan Pezeshgi Modarres, Sanjiv Dhingra, Jiming Kong, Giacomo G. Consalez and Hassan Marzban
Int. J. Mol. Sci. 2021, 22(6), 2994; https://doi.org/10.3390/ijms22062994 - 15 Mar 2021
Cited by 6 | Viewed by 2443
Abstract
Lysosomal acid phosphatase 2 (Acp2) mutant mice (naked-ataxia, nax) have a severe cerebellar cortex defect with a striking reduction in the number of granule cells. Using a combination of in vivo and in vitro immunohistochemistry, Western blotting, BrdU assays, and [...] Read more.
Lysosomal acid phosphatase 2 (Acp2) mutant mice (naked-ataxia, nax) have a severe cerebellar cortex defect with a striking reduction in the number of granule cells. Using a combination of in vivo and in vitro immunohistochemistry, Western blotting, BrdU assays, and RT-qPCR, we show downregulation of MYCN and dysregulation of the SHH signaling pathway in the nax cerebellum. MYCN protein expression is significantly reduced at P10, but not at the peak of proliferation at around P6 when the number of granule cells is strikingly reduced in the nax cerebellum. Despite the significant role of the SHH–MycN pathway in granule cell proliferation, our study suggests that a broader molecular pathway and additional mechanisms regulating granule cell development during the clonal expansion period are impaired in the nax cerebellum. In particular, our results indicate that downregulation of the protein synthesis machinery may contribute to the reduced number of granule cells in the nax cerebellum. Full article
(This article belongs to the Special Issue Cytokines in Lysosomal Storage Diseases)
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