Differential co-expression between α-synuclein and IFN-γ signaling genes across development and in parkinson's disease

Expression patterns of the alphα-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 (rho520.78). In contrast, a metaanalysis 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).