Dystrophic changes of nigrostriatal axons harboring a SYNJ1 Parkinson's mutation suggest catastrophic failure of endocytic mechanisms.

Mutant SYNJ1 causes dystrophic nigrostriatal axons with onion-like plasma membrane infoldings in a Parkinson's mouse model.

• Why it matters: Understanding the cellular basis of Parkinson's disease is crucial, as early neuronal changes may reveal targets for intervention. The role of endocytic failure in dopaminergic neuron degeneration remains unclear, especially in specific axonal populations.
• What they did: Researchers used correlative light microscopy and focused ion beam-scanning electron microscopy (FIB-SEM) to visualize 3D structures in the striatum of mice with the R258Q SYNJ1 mutation, revealing focal axonal dilations with massive plasma membrane infoldings.
• The result: These dystrophic structures are associated with dopamine release deficits, suggesting that endocytic imbalance may contribute to axonal vulnerability and Parkinsonian pathology in this model.