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Bidirectional Relation Between Parkinson'S Disease And Glioblastoma Multiforme

FRONTIERS IN NEUROLOGY(2020)

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Abstract
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 orPARK7. 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.
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Key words
Parkinson's disease,glioblastoma multiforme,pleiotropy,cancer,neurodegeneration
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