Konstantina Tetorou, Artadokht Aghaeipour, Simran Singh, Jennifer E Morgan, Francesco Muntoni. The role of dystrophin isoforms and interactions in the brain. Brain. 2025, Volume 148, Issue 4, Pages 1081–1098

https://academic.oup.com/brain/article/148/4/1081/7914977

This review article explores the role of dystrophin, a protein essential for muscle function, in the brain. While dystrophin is well-known for its connection to Duchenne muscular dystrophy (DMD), it also plays a role in brain development and function. The researchers investigated how different isoforms of dystrophin are distributed in various brain regions and how they interact with other proteins. 

Key findings from the study include:

• Dystrophin Isoforms and Brain Regions: Different isoforms of dystrophin, including Dp427, Dp140, and Dp71, are found in specific brain regions. These isoforms influence how different parts of the brain function, impacting how brain cells communicate.
• Protein Interactions: Dystrophin works alongside other proteins like dystroglycan and syntrophins, forming complexes that are crucial for maintaining stability among brain cells specifically on the synapse. These interactions are particularly important for inhibitory synapses, which regulate brain activity.
• Implications for Neurological Disorders: Changes in dystrophin expression and function may contribute to cognitive and behavioural symptoms in individuals with DMD. Understanding how dystrophin functions in the brain could help develop therapies targeting these symptoms.

Overall, this research enhances our understanding of dystrophin’s role beyond muscles, providing insights into how it supports brain health while interacting with other proteins and how its absence might lead to neurological challenges in DMD.