PD map update – February’19 edition

We are proud to announce a new release of the Parkinson’s disease map. This PD map update introduces an extensive review of the area of neuroinflammation, and introduces mechanisms of insulin signaling. Take a look at the description of changes below.

Curation workshop

In October 2018 we had a productive curation workshop focused on neuroinflammation, neuroprotection and aging. Following the comments we got from our reviewers, we went through the contents of the map and extended it by recent literature findings. The main curator of this edition is Diana Ramirez Ardila from ITTM, supported by our own Ewa Smula in integrating the curated findings into the PD map.

Microglial phagocytosis

We separated existing mechanisms of microglial phagocytosis and combined it with the new content into a separate functional area. You can see it here. It fits well the area of synuclein spreading, as phagocytosis signaling is triggered by synuclein aggregates. There is an interesting signaling module in there as well: dopamine receptors are also present on microglial surfaces and modulate their neuroinflammatory response. Take a look here.

Microglial signaling

Mechanisms linking the angiotensin receptor to Parkinson’s disease and neuroinflammation were introduced here. Additionally, we updated the signaling downstream of Toll-like receptors, especially upstream from the NFkB pathway.

Insulin signaling

We reworked a bit the previous mechanism of IGFR1 signaling. Now the interactions show in more detail both IGFR1 and insulin receptor activation, as well as IRS1, integrator of the two (see here). As in many other places of the map, synuclein is regulating this cascade as well. It happens by activation of the insulin degrading enzyme. The finding we included shows that synuclein oligomers are actually helping with the insulin receptor recycling.

We hope you’ll enjoy this release. A big thank you for Diana Ramirez, for her major contribution to the curation of the content for this release, and to Ewa Smula, for careful introduction of these new bits and pieces into the map. We’re looking forward to your feedback.

Marek Ostaszewski