Academic Journal
Charcot-Marie-Tooth disease variants of HSPB1 progressively alter neuromuscular signalling.
| Τίτλος: | Charcot-Marie-Tooth disease variants of HSPB1 progressively alter neuromuscular signalling. |
|---|---|
| Συγγραφείς: | Aolymat I; Department of Biochemistry, Cell and Systems Biology, ISMIB, University of Liverpool, Liverpool L69 3BX, UK., Barclay JW; Department of Biochemistry, Cell and Systems Biology, ISMIB, University of Liverpool, Liverpool L69 3BX, UK. |
| Πηγή: | Disease models & mechanisms [Dis Model Mech] 2026 Aug 01; Vol. 19 (8). Date of Electronic Publication: 2026 Aug 28. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Company of Biologists Ltd Country of Publication: England NLM ID: 101483332 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1754-8411 (Electronic) Linking ISSN: 17548403 NLM ISO Abbreviation: Dis Model Mech Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Cambridge : Company of Biologists Ltd., c2008- |
| Ιατρικοί όροι (MeSH): | Charcot-Marie-Tooth Disease*/genetics , Charcot-Marie-Tooth Disease*/metabolism , Caenorhabditis elegans*/metabolism , Caenorhabditis elegans*/drug effects , Caenorhabditis elegans*/genetics , Signal Transduction*/drug effects , HSP27 Heat-Shock Proteins*/genetics , HSP27 Heat-Shock Proteins*/metabolism , Caenorhabditis elegans Proteins*/genetics , Caenorhabditis elegans Proteins*/metabolism , Neuromuscular Junction*/metabolism , Neuromuscular Junction*/drug effects , Muscles*/pathology , Muscles*/metabolism , Heat-Shock Proteins*/genetics , Heat-Shock Proteins*/metabolism, Mutation/genetics ; Aging/metabolism ; Aldicarb/pharmacology ; Mutant Proteins/metabolism ; Animals ; Molecular Chaperones ; Animals, Genetically Modified ; Humans |
| Περίληψη: | Autosomal dominant variants in HSPB1 can cause type 2 Charcot-Marie-Tooth disease, a progressive neuromuscular disorder. HSPB1 is a small, ATP-independent chaperone that functions in protein folding, stabilisation and stress protection, as well as regulating intracellular processes such as organization of the cytoskeleton. How diverse variants in HSPB1 exert progressive neuromuscular defects is unclear. Using a transgenic Caenorhabditis elegans model, we examined three distinct HSPB1 variants and determined that mutant HSPB1 caused an early defect in neuromuscular signalling strength as assayed by aldicarb sensitivity. Our data point to the effects being presynaptic in origin and unrelated to differences in expression of mutant HSPB1 compared with that of the wild-type protein. In contrast, the early defect in neuromuscular signalling may be a result of a general loss of small chaperone function. We also identified a progressive effect whereby age-dependent changes to neuromuscular signalling were accelerated in worms expressing mutant HSPB1. These effects were not mirrored by a general loss of small chaperone function; however, wild-type HSPB1 expression strikingly protected against progressive defects seen in controls. These results indicate a possible progressive mechanism for HSPB1-dependent neuromuscular defects. (© 2026. Published by The Company of Biologists.) |
| Competing Interests: | Competing interests The authors declare no competing or financial interests. |
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| Grant Information: | P40 OD010440 United States OD NIH HHS; University of Liverpool; Hashemite University |
| Contributed Indexing: | Keywords: Aldicarb; Charcot–Marie–Tooth disease type 2; Hsp27; Synaptic transmission |
| Substance Nomenclature: | 0 (HSP27 Heat-Shock Proteins) 0 (Caenorhabditis elegans Proteins) 0 (Molecular Chaperones) 8V071SH05P (Aldicarb) 0 (Heat-Shock Proteins) 0 (Mutant Proteins) |
| Entry Date(s): | Date Created: 20260723 Date Completed: 20260828 Latest Revision: 20260918 |
| Update Code: | 20260918 |
| PubMed Central ID: | PMC13580553 |
| DOI: | 10.1242/dmm.052805 |
| PMID: | 42489084 |
| Βάση Δεδομένων: | MEDLINE |
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