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Šoltić, D and Fuller, HR (2020) Molecular crosstalk between non-SMN-related and SMN-related spinal muscular atrophy. Neuroscience Insights, 15. ISSN 2633-1055
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Abstract
Most cases of spinal muscular atrophy are caused by functional loss of the survival of motor neuron 1 (SMN1) gene, while less than 5% of cases are attributed to genes other than SMN. Mutations in LMNA, the lamin A/C encoding gene, cause an adult form of SMA, and in our recent work we highlight a role for lamin A/C in SMN-related SMA pathways. Here, we discuss this apparent molecular crosstalk between different types of SMA in context with previous work, showing that dysregulation of proteins produced by other SMA-causing genes, including UBE1, GARS
and SETX, are also implicated in SMN-related SMA pathways. The perturbation of UBE1, GARS and lamin A/C help explain mechanisms of tissue-specific pathology in SMA, and we propose Wnt/β-catenin signalling as a common molecular pathway upon which they each converge. Therapeutic strategies directed at these proteins, or their convergent pathways, may therefore offer a new approach to targeting tissue-specific pathology in SMN-related SMA.
Item Type: | Article |
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Additional Information: | The final version of this article and all relevant information can be found at; https://journals.sagepub.com/doi/10.1177/2633105520914301 |
Uncontrolled Keywords: | Spinal Muscular Atrophy, SMA, SMN, LMNA, Lamin A/C, GARS, UBE1, UBA1, SETX, β-catenin, Wnt/β-catenin |
Subjects: | R Medicine > R Medicine (General) R Medicine > RS Pharmacy and materia medica R Medicine > RZ Other systems of medicine |
Divisions: | Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering |
Depositing User: | Symplectic |
Date Deposited: | 03 Mar 2020 15:27 |
Last Modified: | 18 Aug 2020 09:47 |
URI: | https://eprints.keele.ac.uk/id/eprint/7748 |