LRRK2 regulates synaptic function through modulation of actin cytoskeletal dynamics.

Lrrk2 loss disrupts BDNF-dependent synaptic modulation and actin cytoskeleton dynamics, revealing a key pathway in Parkinson's disease pathophysiology.

• Why it matters: Understanding early synaptic alterations is crucial because they precede neuronal loss in PD, yet remain poorly characterized, hindering early intervention strategies.
• What they did: The study combined literature meta-analysis, multi-omics, and experimental techniques in Lrrk2 mouse models and human iPSC-derived neurons, examining over 100 proteins and signaling pathways involved in synapse and actin regulation.
• The result: Findings show LRRK2 influences BDNF signaling and actin remodeling at synapses, with LRRK2 deficiency impairing synaptic maturation and structure, thus highlighting potential targets for early PD therapies.