In Parkinson's disease, so-called Lewy bodies, which consist primarily of the protein ⍺-synuclein, accumulate in certain regions of the brain. As a result, nerve cells die off. This is related to a non-functional elimination mechanism. Ubiquitin-controlled protein degradation must occur in order for the harmful Lewy bodies to be removed. For this purpose, the Lewy bodies must be labeled by the attachment of linear polyubiquitin chains; therefore, a proteasome is formed that can be degraded by autophagy.

Using tissue from deceased Parkinson's patients and additionally in cell cultures, the team was able to show that the protein NEMO interacts with the autophagy process by docking to the complex of linear ubiquitin chains and another protein called p62 and promoting the degradation of ⍺-synuclein.

The scientists now want to develop new therapeutic strategies based on their findings.

Original publication:
Furthmann, N., Bader, V., Angersbach, L. et al. NEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62. Nat Commun 14, 8368 (2023). https://www.nature.com/articles/s41467-023-44033-0

Further source:
https://news.rub.de/english/press-releases/2023-12-19-parkinsons-disease-when-cellular-waste-collector-doesnt-show