An Hspa8 variant is a shocking modifier of spinal muscular atrophy in mice

Article Genetics & Heredity

Epigenetic regulation of plastin 3 expression by the macrosatellite DXZ4 and the transcriptional regulator CHD4

Eike A. Strathmann et al.

Summary: Dysregulated PLS3 levels are associated with various skeletal and neuromuscular disorders as well as common types of solid and hematopoietic cancer. PLS3 overexpression provides protection against spinal muscular atrophy. However, the mechanisms that regulate PLS3 expression are still unknown. In this study, we found that PLS3 escapes X chromosome inactivation and that the copy number of DXZ4 monomers correlates significantly with PLS3 levels. We also identified CHD4 as an epigenetic transcriptional regulator of PLS3, suggesting a multilevel epigenetic regulation that may contribute to the dysregulation of PLS3 in disease.

AMERICAN JOURNAL OF HUMAN GENETICS (2023)

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Article Neurosciences

A spinal muscular atrophy modifier implicates the SMN protein in SNARE complex assembly at neuromuscular synapses

Jeong-Ki Kim et al.

Summary: Scientists have discovered a synaptic chaperone variant called Hspa8G470R that can suppress spinal muscular atrophy (SMA) and improve neuromuscular function in model mice. The variant alters SMN2 splicing and stimulates the formation of a tripartite chaperone complex critical for synaptic homeostasis. This study provides new insights into how deficiency of the SMN protein causes motor neuron disease.

NEURON (2023)

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Article Biochemistry & Molecular Biology

What Genetics Has Told Us and How It Can Inform Future Experiments for Spinal Muscular Atrophy, a Perspective

Anton J. Blatnik et al.

Summary: Proximal spinal muscular atrophy (SMA) is a genetic disorder characterized by motor neuron loss and skeletal muscle atrophy due to deficiency of the essential survival motor neuron (SMN) protein. Therapeutics aimed at increasing SMN protein levels have shown efficacy in treating SMA, but the mechanisms underlying motor neuron loss are still not well understood. Genetics and biochemistry have provided insights into SMA and SMN, from identifying genetic regions to developing potential treatments, but further research is needed to determine critical pathways in SMA.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Genetics & Heredity