Elsevier Inc. vesicular trafficking PD 6 PD 7 PD 20 transcriptional modulation neuromelanin Fe3+ ---- neuromelanin complex architecture Ca2+ calcium homeostasis pathway pacemaker activity donwregulated miRNA ---> upregulated target translation potential PD miRNA ---> Parkinson Disease (PD) upregulated miRNA ---> downregulated target translation downregulated target translation upregulated miRNA donwregulated miRNA upregulated target translation PD 8 PD 1 Snca ---> PD 1 PD 17 autosomal dominant PD sporadic PD autosomal recessive PD Vps35 Synj1 other PD related proteins Pink1 Park2 respiratory complex I Lrrk2 Park7 Lrrk2 ---> Lrrk2 Rab substrates altered mitochondrial autophagy pathway ---| mitochondria dynamics pathway Lrrk2 ---| chaperone mediated autophagy pathway Snca ---| chaperone mediated autophagy pathway Snca ---| DNA modification pathway Snca ---| unfolded protein response pathway Snca ---| respiratory complex I Dnmt1 Snca unfolded protein response pathway electron transport chain pathway Snca ---> mitochondria dynamics pathway loss of DA neurons in SNc mitochondria function Park7 interacting proteins altered mitochondria homeostasis pathway ---> Parkinson Disease (PD) ROS ---> Parkinson Disease (PD) Parkinson Disease (PD) altered mitochondria homeostasis pathway altered mitochondria dynamics pathway Fe2+ ---- Fe3+ Fe2+ Fe3+ Wnt signaling, canonical pathway Wnt signaling, canonical pathway ---> dopaminergic neuron mitochondria dynamics pathway altered mitochondrial autophagy pathway Lrrk2 interacting proteins Park2 ---> autosomal recessive PD lysosomal function endocytosis Park7 ---> anti-oxidant anti-oxidant Park7 ---> transcriptional modulation altered retromer-mediated pathway ---> Parkinson Disease (PD) altered retromer-mediated pathway altered clathrin-dependent synaptic vesicle endocytosis Lrrk2 ---> PD 8 Lrrk2 ---> sporadic PD Pink1 ---> PD 6 Park7 ---> PD 7 Lrrk2 ---> mitochondria function Lrrk2 ---> cytoskeletal system cytoskeletal system Lrrk2 ---> immune system Lrrk2 ---> vesicular trafficking Lrrk2 ---- Lrrk2 interacting proteins mitochondria dynamics pathway ---> altered mitochondria dynamics pathway Park7 ---> mitochondria function Snca ---> mitochondria function Vps35 ---> PD 17 Synj1 ---> PD 20 Snca ---> sporadic PD altered clathrin-dependent synaptic vesicle endocytosis ---> Parkinson Disease (PD) Park7 ---- Park7 interacting proteins dopaminergic neuron immune system altered mitochondria dynamics pathway ---> altered mitochondria homeostasis pathway calcium homeostasis pathway ---> Parkinson Disease (PD) potential PD miRNA Snca ---> synaptic vesicle homeostasis Snca interacting proteins Snca ---- Snca interacting proteins synaptic vesicle homeostasis DNA modification pathway Dnmt1 ---- Snca chaperone mediated autophagy pathway ROS Lrrk2 Rab substrates