Overview
- A team from CONICET and University Grenoble Alpes reports that levodopa is enzymatically attached to the C-terminus of alpha-tubulin, forming L-Dopa–modified microtubules.
- These modified polymers show altered dynamics with more frequent disassembly and reduced entry into dendritic spines in mouse neuronal cultures.
- Cultures containing the modified microtubules exhibit lower density of mature spines and fewer excitatory synapses, indicating weakened connectivity.
- Incorporated levodopa resists removal and disrupts the tubulin tyrosination–detyrosination cycle, leading to accumulation and persistence.
- Genetically engineered neurons unable to incorporate levodopa did not lose spines or synapses, and the authors emphasize the preclinical nature of the findings and continued importance of levodopa therapy, as reported in npj Parkinson's Disease.