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Cancer and Parkinson's disease (PD) define two disease entities that include opposite concepts. Indeed, the involved mechanisms are at different ends of a spectrum related to cell survival - one due to enhanced cellular proliferation and the other due to premature cell death. There is increasing evidence indicating that patients with neurodegenerative diseases like PD have a reduced incidence for most cancers. In support, epidemiological studies demonstrate an inverse association between PD and cancer. Both conditions apparently can involve the same set of genes, however, in affected tissues the expression was inversely regulated: genes that are down-regulated in PD were found to be up-regulated in cancer and vice versa, for example p53 or PARK7 . When comparing glioblastoma multiforme (GBM), a malignant brain tumor with poor overall survival, with PD, astrocytes are dysregulated in both diseases in opposite ways. In addition, common genes, that are involved in both diseases and share common key pathways of cell proliferation and metabolism, were shown to be oppositely deregulated in PD and GBM. Here, we provide an overview of the involvement of PD- and GBM-associated genes in common pathways that are dysregulated in both conditions. Moreover, we illustrate why the simultaneous study of PD and GBM regarding the role of common pathways may lead to a deeper understanding of these still incurable conditions. Eventually, considering the inverse regulation of certain genes in PD and GBM will help to understand their mechanistic basis, and thus to define novel target-based strategies for causative treatments., (Copyright © 2020 Mencke, Hanss, Boussaad, Sugier, Elbaz and Krüger.)

CRISPR-Cas9 mediated gene editing in induced pluripotent stem cells became an efficient tool to investigate biological mechanisms underlying genetic-driven diseases while accounting for the respective genetic background. This technique relies on the targeting of a specific nucleotide sequence present in the gene of interest. Therefore, the gene editing of some genes can be complicated by non-coding pseudogenes presenting a high homology of sequence with their respective genes. Among them, GBA is raising special interest because of its implication as the most common genetic risk factor for Parkinson's disease. In this study, we present an easy-to-use CRISPR-Cas9 gene editing strategy allowing for specific editing of point mutations in a gene without genetic alteration of its pseudogene exemplified by the correction or insertion of the common N370S mutation in GBA . A quality control strategy by combined fluorescence and PCR-based screening allows the early identification of correctly edited clones with unambiguous identification of the status of its pseudogene, GBAP1 . Successful gene editing was confirmed by functional validation. Our work presents the first CRISPR-Cas9 based editing of a point mutation in GBA and paves the way for technically demanding gene engineering due to the presence of pseudogenes., (Copyright © 2020 Hanss, Boussaad, Jarazo, Schwamborn and Krüger.)