04/04/2016 - RGD releases an updated interactive diagram page for the Parkinson disease pathway

Parkinson disease pathway

Parkinson’s disease (PD) is a progressive neurodegenerative condition of complex etiology exhibiting a range of movement syndromes caused by the selective degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). It is the second most prevalent neurodegenerative disease and is largely sporadic, with age representing a major risk factor. Several culprit genes and associated pathways play roles in the condition while other PD genes are still to be functionally characterized. Mitochondrial function declines with age. Alterations in mitochondrial function and homeostasis and alterations in other, related or important pathways can contribute to PD unfolding. Effects are likely augmented by the unique features of dopaminergic neurons in this brain area. 

Updates: Rab GTPases have been identified as substrates of LRKK2, which are different from the Rabs identified as interacting partners. Phosphorylation of Rabs affects their interaction with several regulators. Two of the Rab substrates are also interacting partners for SNCA. As in the case of other interactions and modifications reported for PD-associated genes, the exact implications of these findings for PD remain to be established but they point to the complexity of the system. They also underscore the possible role of LRKK2 in vesicular trafficking. Click here to explore aspects of this still enigmatic system.