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Title: | Lysosomal enzymes and their role in Charcot-Marie-Tooth disease type 1A | Authors: | LIBBERECHT, Karen VANGANSEWINKEL, Tim DIRKX, Nathalie Hasevoets, S. VAN DEN BOSCH, Jolien JEURISSEN, Hanne LAMBRICHTS, Ivo Van den Bosch , Ludo WOLFS, Esther |
Issue Date: | 2022 | Publisher: | WILEY | Source: | JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, 27 , p. S169 -S170 | Abstract: | Charcot-Marie-Marie Tooth disease type 1A (CMT1A) is the most common demyelinating peripheral neuropathy. CMT1A is caused by a duplication of the peripheral myelin protein 22 (PMP22) gene. The exact mechanism causing dysfunctional Schwann cells is yet to be defined, however, disrupted proteostasis due to PMP22 aggregation has been described previously. Lysosomes are key degradative compartments in protein homeostasis by digesting misfolded proteins via enzymes such as cathepsins. A disruption in proteostasis and cathepsins has been reported in several neurodegenerative diseases such as Alzheimer's Disease and Parkinson's Disease. Nevertheless, cathepsin alterations in CMT1A have not been explored yet. To elucidate cathepsin levels in CMT1A, we monitored cathepsin D (CTD), B (CTB) and S (CTS) expression levels in nerves of 1-, 2-, 4-, 8-and 52-week old C3-PMP22 and WT mice. For CTD, CTB and CTS, an increased expression was visible starting in 2-week old CMT1A mice, persisting until the age of 52 weeks. CTD levels increased significantly at 4-(103%, p=0.04) and 8-week-old (240%, p=0.02) CMT1A mice, and remained increased in 52-week-old mice (123%, p=0.16). CTS gene expression levels were significantly higher at the age of 4 weeks (92%, p=0.01), and its increase was still visible at 8 weeks (57%, p=0.55) and 52 weeks (48%, p=0.99). CTB expression was observed to be increased in 4-(65%, p=0.08) and 8-week old mice (213%, p= 0.07), and was significantly increased in 52-week old mice (p=0.04, 123%). Taken together, we observed an increased gene expression of cathepsins in C3-PMP22 mice compared to WT starting in 2 week-old-mice, peaking at 4-8 weeks and continuing to be visible at the age of 52 weeks. Nevertheless, further research is crucial to explore the consequences of these lysosomal enzyme changes in CMT1A. | Keywords: | Charcot-Marie-Tooth;Schwann cells;lysosomes | Document URI: | http://hdl.handle.net/1942/37908 | ISSN: | 1085-9489 | e-ISSN: | 1529-8027 | ISI #: | 000822950200351 | Category: | M | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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PNS2022_Abstract_KarenLibberecht_.pdf Restricted Access | Published version | 148.42 kB | Adobe PDF | View/Open Request a copy |
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