L-Dopa-modified microtubules lead to synapse instability in cultured neurons: possible implications in Parkinson's disease therapy.

ABSTRACT: L-Dopa, the main Parkinson's disease treatment, unexpectedly alters the postsynaptic architecture of cultured mouse neurons through its incorporation into α-tubulin via tubulin tyrosine ligase (TTL). This leads to the formation of L-Dopa-modified microtubules, with impaired dynamics and reduced entry into dendritic spines, increasing their vulnerability to pruning. As a result, dendritic spine density-particularly mature spines-and the number of excitatory synapses are significantly reduced. L-Dopa-mediated synaptic defects are absent in neurons lacking the ability to incorporate it into α-tubulin-TTL or SVBP knockout neurons-confirming a microtubule-dependent mechanism. In vitro, L-Dopa-modified tubulin interfered with VASH1-SVBP activity, the major brain's tubulin carboxypeptidase, poten

SUBMITTER: Zorgniotti A 

PROVIDER: S-EPMC12534460 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature