PD map meets the Community at the 2nd PD workshop

The PD map had its second encounter with the community. A curation workshop happened again, what is extremely important. Continuity is critical to keep the map fresh, and in use. This time we met for the workshop during the “2nd International Parkinson's Disease Symposium” in Munsbach, Luxembourg.

 

Continuity

The workshop in Luxembourg had more focus than the first one, held in Geneva (see PD map meets the Community). There, we made a broad invitation to join the community curation. Here, on top of the broadcast, we invited experts to help us to pinpoint the key mechanisms that are still missing in the map. What was similar between the two workshops? The excitement from sharing knowledge on PD molecular mechanisms. Also, the outcomes of the workshop were presented during the symposium, a day later.

How did it look like? Some fifty people at seven tables discussed specific pathways implicated in PD (see the list of participants). Moderators carefully noted down the suggestions to add, extend and correct the content of the PD map. In particular, the following mechanisms were curated. 

 

α-synuclein pathobiology

We focussed on mechanisms of synuclein degradation via the lysosomal pathway. Especially, chaperone-mediated autophagy was discussed, as well as lysosomal PD genes: GBA1 and ATP13A2.

 

Mitochondrial (dys)function

We critically discussed the concept of mitochondrial function and dysfunction. Topics discussed in particular were mitophagy, regulation of dynamics and transport, control of apoptotic pathway and a novel concept of Mitochondrial Derived Vesicles (see Faster than mitophagy). It was suggested that the PD map considers the “baseline” of mitochondrial function – to maintain ATP production.

 

Synaptic (dys)function

The discussion started with review of PD genes associated with synaptic dysfunction. We then reviewed the synaptic mechanisms implicated in the PD map. Finally, we focused on proteins and pathways implicated in axonal degeneration [PMID:17311006], and on synaptic signaling pathways [PMID:22026965]. 

 

Calcium signalling

In this group, we discussed a number of PD pathways where calcium is implicated, including axonal transport, inflammation and apoptosis. We identified a number of Ca2+ channels that should be implemented in the map, including Cav1.1 [PMID:23771339].

 

Neuroinflammation

We decided to focus on one aspect of neuroinflammation in PD, namely microglia activation by synuclein. In this context, we suggested improvements in representation of toll-like and adenosine receptors, as well as implementation of complement 3 and interferon-gamma pathways.

 

Oxidative stress

This group discussed implication of oxidative and especially nitrosative stress in PD-related pathways. First, the representation of nitrosative stress-induced modifications of relevant proteins such as α-synuclein [PMID:23452040] was reviewed. After that special attention was paid to DJ-1, an important oxidative stress sensor and effector, active in different cellular compartments and processes [PMID:23766857]. Finally a brainstorming was performed on the most relevant source of oxidative stress that may initiate the cascade of PD pathogenesis. Here mitochondrial dysfunction was identified as the hottest candidate. 

 

Functionality

During this meeting, we also got a number of requests to improve the functionality of the map. The main suggestion was to improve the visualization of the map by demonstrating high-level organization levels in symbols of neurobiology (drawings of neuron, compartments, spatial distribution of pathways) rather than computational biology (networks). Another was the possibility to display submaps, or mark “open questions” in the map that then could be curated by the users. Finally, we were asked to provide “confidence score” to the interactions of the map, to quickly distinguish well-defined and less-explored areas of the map.

 

It is very important to have a meaningful continuation of the community curation of PD pathways, and to support it by developing the PD map. We were very happy and excited to see a ton of excitement and satisfaction from this meeting. It was deeply motivating to see how an engaged community can improve the understanding of a complex picture by sharing knowledge and expertise. Thanks a lot to all the participant for their highly valuable contributions. Again, we have a lot of important homework to do. You will hear more from us.

 

Marek Ostaszewski

Curator/Developer

 

Organization of this event was possible due to generous support of 

L'Oeuvre Nationale de Secours Grande-Duchesse Charlotte.

We are extremely grateful for your help! Thank you!

 

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