Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons.

ABSTRACT: The end-stage pathology of Parkinson's disease (PD) involves the loss of dopamine-producing neurons in the substantia nigra pars compacta (SNc). However, synaptic deregulation of these neurons begins much earlier. Understanding the mechanisms behind synaptic deficits is crucial for early therapeutic intervention, yet these remain largely unknown. In the SNc, different dopamine neuron subtypes show varying susceptibility patterns to PD, complicating our understanding. This study uses intersectional genetic mouse models to uncover synaptic perturbations in vulnerable dopamine neurons, focusing on the LRRK2 kinase, a protein closely linked to PD. Through a combination of immunofluorescence and advanced proximity labeling methods, we found higher LRRK2 expression in the most vulnerable dopamin

SUBMITTER: Chen C 

PROVIDER: S-EPMC12407872 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature