Tuesday, 20 September 2022 18:48

Research into Parkinson's disease: New protein could inhibit protein deposits Featured

In cell culture, researchers from Philadelphia have discovered a new mechanism that could inhibit the deposition of the feared alpha-synuclein.

So-called genome-wide association studies are used to identify risk genes that can lead to Parkinson's disease. The researchers have used this technique to study a site on the 7th chromosome that is associated with the risk of Parkinson's disease. In doing so, they discovered a transmembrane protein called GPNMB (glycoprotein non-metastatic melanoma protein B). The glycoprotein NMB is upregulated, for example, in macrophages when they interact with tumor cells, but is also produced by neurons in the brain where it is involved in the transport of molecules across the cell membrane.

In human brain samples both from Parkinson's cases and from neurologically normal controls for comparison, they were able to confirm that a threefold higher GPNMB expression was present in Parkinson's patients. In human neurons derived from pluripotent stem cells, confocal microscopy revealed that loss of GPNMB was associated with a marked reduction in α-synuclein (aSyn) at the synapse.

GPNMB could be a candidate for biomarker development as well as a therapeutic target in Parkinson's disease.

Original publication:
Diaz-Ortiz ME, Seo Y, Posavi M, Carceles Cordon M, Clark E, Jain N, Charan R, Gallagher MD, Unger TL, Amari N, Skrinak RT, Davila-Rivera R, Brody EM, Han N, Zack R, Van Deerlin VM, Tropea TF, Luk KC, Lee EB, Weintraub D, Chen-Plotkin AS. GPNMB confers risk for Parkinson's disease through interaction with α-synuclein. Science. 2022 Aug 19;377(6608):eabk0637. doi: 10.1126/science.abk0637. Epub 2022 Aug 19. PMID: 35981040.