Project description:We compared transcriptome of monocyte-derived macrophages of 5 patients with GBA-PD (4 L444P/N, 1 N370S/N) and 4 asymptomatic GBA mutation carriers (GBA-carriers) (3 L444P/N, 1 N370S/N) and 4 controls. We also conducted comparative transcriptome analysis for L444P/N only GBA-PD patients and GBA-carriers. Revealed deregulated genes in GBA-PD independently of GBA mutations (L444P or N370S) were involved in immune response, neuronal function. We found upregulated pathway associated with zinc metabolism in L444P/N GBA-PD patients. The potential important role of DUSP1 in the pathogenesis of GBA-PD was suggested.
Project description:We compared transcriptome of monocyte-derived macrophages of 5 patients with GBA-PD (4 L444P/N, 1 N370S/N) and 4 asymptomatic GBA mutation carriers (GBA-carriers) (3 L444P/N, 1 N370S/N) and 4 controls. We also conducted comparative transcriptome analysis for L444P/N only GBA-PD patients and GBA-carriers. Revealed deregulated genes in GBA-PD independently of GBA mutations (L444P or N370S) were involved in immune response, neuronal function. We found upregulated pathway associated with zinc metabolism in L444P/N GBA-PD patients. The potential important role of DUSP1 in the pathogenesis of GBA-PD was suggested.
Project description:To investigate the contribution of Mincle in neuronopathic Gaucher disease, we established Gba flox/flox; Nestin-Cre mice and crossed them with Mincle deficient mice. RNA sequencing of microglia from these mice revealed Axl, a phaogocytic receptor was upregulated in Gba flox/flox; Nestin-Cre mice. In addition, Tnf was upregulated in Gba flox/flox; Nestin-Cre mice in a Mincle-dependent manner. Our further study elucidated that Mincle, Axl and TNF are involved in the pathology of Gaucher disease.
