Exploring dysfunctional cellular mechanisms in neuro-degenerative diseases provides insight to mechanism of the disorder. The paper demonstrated a novel interatcion between LRRK2 and auxilin genes and how they bring about dopamine mediated toxicity in PD.
Synaptic vesicle pools are recovered at the axon terminal through clathrin mediated endocytosis. This entire process is tightly controlled by phosphoregulated proteins. After pinching off, auxilin binds to a new clathrin coated vesicle and recruits hsc70 to remove the clathrin clutch. This results in producing a synaptic vesicle that can be packaged with neurotransmitters.
Defective synaptic vesicle endocytosis in substantia nigra pars compacta dopaminergic neurons couldead to increased levels of cytosolic dopamine. These excess dopamine get oxidised and trigger a cascade of toxic effects. The study demonstrated that LRRK2 mediated phosphorylation of auxin at Ser627 location in a clathrin coated vesicle disrupts endocytosis process. This will result in lot many uncoated vesicles in pre-synaptic terminal and reduced functional synaptic vesicle density.
1. The mutant LRRK2 gene which sits in 12th chromosome in humans is a concern for google CEO, Sergey Brin.
2. When a resupply mission lifts off in August bound for the International Space Station, it will be carrying an important cargo for researchers studying Parkinson’s disease: A protein considered to be a key to potential future therapies