Science PD Mechanism New Discovery: GPNMB drives pathological progression by promoting α-syn internalization

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Parkinson's disease (PD) is a progressive neurodegenerative disease affected by

Recently, Alice S.

Multiple GWASs have linked chromosome 7 loci (rs199347) to PD, combined with GTEx databases [1, 2] and co-localization analysis, and the authors found that GPNMB exhibited the greatest overlap

Although studies have shown that GPNMB enhances the malignant phenotype of many cancers, there are few

Since GPNMB is necessary for α-Syn internalization, does its deletion save these cells from the pathological progression of α-Syn? To this end, the authors introduced α-Syn PFFs into three cell culture media, and after the end of the culture, a large number of S129 phosphorylated α-Syn were present in WT neurons, and the degree of insoluble α-Syn aggregates was much more severe, which had a dense appearance and were more common in the periphery

For the study, Brit Mollenhauer and Christine A.

Model Maker: Eleven

References

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Nalls et al.
, Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: A metaanalysis of genome-wide association studies.
Lancet Neurol.
18, 1091–1102 (2019).
doi: 10.
1016/S1474-4422(19)30320-5; pmid: 31701892

2.
GTEx Consortium, Genetic effects on gene expression across human tissues.
Nature 550, 204–213 (2017).
doi: 10.
1038/ nature24277; pmid: 29022597

3.
O.
Mayba et al.
, MBASED: Allele-specific expression detection in cancer tissues and cell lines.
Genome Biol.
15, 405 (2014).
doi: 10.
1186/s13059-014-0405-3; pmid: 25315065

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