Disrupted extracellular matrix and cell cycle genes in autism-associated Shank3 deficiency are targeted by lithium

Shank3 and Phelan-McDermid Syndrome (PMDS)


  • The Shank3 gene plays a crucial role in brain development and function.
  • Mutations in Shank3 cause Phelan-McDermid Syndrome (PMDS), a genetic disorder characterized by autism spectrum disorder (ASD), intellectual disability, and seizures.


Effects of Shank3 deficiency on gene expression


  • Shank3 deficiency disrupts the expression of many genes, including those related to the extracellular matrix (ECM) and cell cycle.
  • The ECM provides structural support for cells and tissues, while the cell cycle controls cell division.
  • Disruptions in these genes likely contribute to the symptoms of PMDS.


Lithium treatment for PMDS


  • Lithium is a medication used to treat mood disorders like bipolar disorder.
  • Studies have shown that lithium can improve symptoms of PMDS, including social communication and repetitive behaviors.


How lithium works in PMDS


  • The article suggests that lithium may work by reversing the effects of Shank3 deficiency on ECM and cell cycle genes.
  • This finding suggests that targeting these genes may be a new approach for treating PMDS.


Future directions


  • The authors call for further research to investigate the mechanisms by which lithium works in PMDS and to develop new therapies that target ECM and cell cycle genes.



What is the Shank3 gene?


The Shank3 gene encodes the major postsynaptic scaffolding protein SHANK3. Mutations in this gene cause Phelan-McDermid Syndrome (PMDS), a syndromic form of autism spectrum disorder (ASD).


What are the symptoms of PMDS?


PMDS is characterized by global developmental delay, intellectual disorders (ID), ASD behavior, affective symptoms, as well as extra-cerebral symptoms.


How does lithium affect Shank3 deficiency?


Lithium treatment has been shown to have a rescue-like effect on the ECM and cell cycle gene sets in Shank3 deficient cells. This suggests that lithium may be a potential drug for the treatment of PMDS.


What are the findings of this study?


This study found that the Shank3Δ11(−/−) genotype affected the overall transcriptome, with extracellular matrix (ECM) and cell cycle transcriptional programs being disrupted. Lithium treatment was able to rescue these effects.


What are the implications of this study?


These findings suggest that the ECM compartment and cell cycle genes may be new players in the pathophysiology of Shank3 deficiency, and that lithium may be a potential treatment for PMDS.



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