Seminar: Unraveling the connection between SPN1-related muscular dystrophy, SMN instability, and autophagy dysfunction by Dr. Marvan Nashabat
On September 11, 2025 at 11:00 am, we are hosting Dr. Marvan Nashabat, who will give a seminar titled “Unraveling the connection between SPN1-related muscular dystrophy, SMN instability, and autophagy dysfunction” at IBG Aziz Sancar Auditorium.
Dr. Nashabat earned his PhD at the Department of Cellular and Molecular Medicine at Koç University. His doctoral research focuses on clinical and functional characterization of a new muscular dystrophy caused by novel recessive SNUPN pathogenic variants, which was recently published in Nature Communications.
We welcome your participation to the seminar!
Seminar Abstract
Snurportin-1 (SPN1)-related muscular dystrophy (MD), also known as limb-girdle muscular dystrophy type R29, is a recently recessive disorder characterized by progressive muscle weakness and neurological manifestations. SPN1 directs the import complex, including UsnRNPs and the SMN complex, to nuclear Cajal bodies. We previously demonstrated that SPN1 deficiency disrupts spliceosomal machinery, leading to muscular fiber defects. Given that SMN defects are associated with spinal muscular atrophy (SMA) and contribute to muscular degeneration, mitochondrial dysfunction, and autophagy impairment, we investigated the direct impact of SPN1 deficiency on SMN stability and autophagy regulation.
We demonstrated that SPN1 deficiency significantly reduced SMN protein levels and altered its localization. Transcriptomics analyses revealed alternative splicing defects and dysregulation of key autophagy-related genes. Impaired autophagic flux was confirmed by dysregulated P62 and LC3II protein levels across all SPN1 mutant models. Treatment with chloroquine and autophagy activation via rapamycin further validated this impairment. Furthermore, mitochondrial markers indicated that SPN1 is essential for proper mitochondrial clearance suggesting a critical role in mitophagy.
In conclusion,SPN1 deficiency appears to destabilize SMN protein and disrupt autophagic flux, revealing a previously unrecognized functional overlap between SPN1-related-MD and SMA pathology. These findings highlight potential therapeutic targets aimed at restoring SMN stability and autophagy homeostasis.