title: Differential Co-Expression between α-Synuclein and IFN-γ Signaling Genes across Development and in Parkinson's Disease.
abstract: Expression patterns of the alpha-synuclein gene (SNCA) were studied across anatomy, development, and disease to better characterize its role in the brain. In this postmortem study, negative spatial co-expression between SNCA and 73 interferon-γ (IFN-γ) signaling genes was observed across many brain regions. Recent animal studies have demonstrated that IFN-γ induces loss of dopamine neurons and nigrostriatal degeneration. This opposing pattern between SNCA and IFN-γ signaling genes increases with age (rho = -0.78). In contrast, a meta-analysis of four microarray experiments representing 126 substantia nigra samples reveals a switch to positive co-expression in Parkinson's disease (p<0.005). Use of genome-wide testing demonstrates this relationship is specific to SNCA (p<0.002). This change in co-expression suggests an immunomodulatory role of SNCA that may provide insight into neurodegeneration. Genes showing similar co-expression patterns have been previously linked to Alzheimer's (ANK1) and Parkinson's disease (UBE2E2, PCMT1, HPRT1 and RIT2).
authors.affiliation: The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar Ilan University, Ramat Gan, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Liscovitch
authors.affiliation: Rotman Research Institute, Baycrest Hospital, Toronto, Ontario, Canada.
authors.forename: Leon
authors.initials: L
authors.lastname: French
mesh_terms: D000367:Age Factors; D001921:Brain / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007371:Interferon-gamma / Q000378:metabolism* / Q000502:physiology; D010300:Parkinson Disease / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D013378:Substantia Nigra / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism* / Q000502:physiology
chemical_list: D051844:alpha-Synuclein; D007371:Interferon-gamma