MDS 2025 | Key emerging data and evolving concepts in prion-like mechanisms of proteinopathies

We have this idea that during disease progression, there is the spreading of pathology in the brain and even from the brain to the periphery or the periphery to the brain. And we don’t know exactly how the protein spreads and if there is actual spreading or just some pathological alteration in the cells that causes the protein to aggregate. So there have been different studies on this topic, and we continue to make progress. But I would highlight again that study that suggests that maybe there’s spreading of pathology from the kidney to the brain just as an alternative possibility. There was also another recent study showing that there is maybe different types of disease progression. One was called brain first, the other gut first. And now there seems to be different possibilities for spreading from sympathetic neurons that innervate the heart or the periphery to the brain and also from parasympathetic neurons to the brain. So there’s constantly new studies coming up and suggesting that we still need to understand more. And then also in detail, we need to understand how the alpha-synuclein protein goes from one cell to the next to induce a pathological alteration. So this is something we still don’t know in detail. A lot of colleagues are investigating this process and looking at extracellular vesicles to understand if these can be carriers of the pathological forms of alpha-synuclein. Other colleagues are investigating these very tiny tubes that connect cells called tunneling nanotubes, and they seem to be also one possible route for the passage of alpha-synuclein from one cell to the next. But there’s other possibilities and we need to continue to investigate to really have an idea of how we will be able to interfere with the transfer of protein and with the spreading of pathology.

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