Targeted kinase inhibition relieves slowness and tremor in a Drosophila model of LRRK2 Parkinson’s disease

The proboscis extension response (PER) of Drosophila. a The PER takes place when sugar-sensitive (Gr5a) neurons on the legs respond (step 1) and signal to the sub-esophageal zone of the CNS (SEZ, step 2). This leads to activation of the E49 motoneurons for the proboscis extension muscle (step 3), muscle contraction (step 4), and extension of the proboscis (step 5). In the sub-esophageal zone, the neuronal signal is modulated by a dopaminergic neuron, TH-VUM, and by other inputs from CNS neurons, possibly including other dopaminergic neurons. b Schematic neural circuit, showing the modulation of the sensory neuron–interneuron–motoneuron axis by TH-VUM. Other interneurons also modulate the proboscis extension response, as reviewed recently.17 a Modified after refs. 52,53; b after refs. 14,15,1