Molecular crosstalk between non-SMN-related and SMN-related spinal muscular atrophy

Šoltić, D; Fuller, H

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/ß-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.

Citation

Šoltić, D., & Fuller, H. (2020). Molecular crosstalk between non-SMN-related and SMN-related spinal muscular atrophy

• Acceptance Date: Mar 2, 2020
• Publication Date: Mar 30, 2020
• Journal: Neuroscience Insights
• Print ISSN: 2633-1055
• Keywords: Spinal Muscular Atrophy, SMA, SMN, LMNA, Lamin A/C, GARS, UBE1, UBA1, SETX, ß-catenin, Wnt/ß-catenin
• Publisher URL: https://doi.org/10.1177%2F2633105520914301