| Abstract: | Niemann-Pick type C disease (NP-C) is a rare and ultimately fatal lysosomal storagedisorder with variable neurologic symptoms. Loss of neuronal function and neuronal celldeath occur in the NP-C brain, similar to the findings for other neurodegenerativediseases. Targeting of neuronal cells in the brain therefore represents a potentialclinical intervention strategy to reduce the rate of disease progression and improve thequality of life. We previously reported that bone marrow stem cells show a neurogeniceffect through CCL2 (also known as monocyte chemoattractant protein-1, MCP-1) secretion inthe brains of NP-C mice. However, the direct effect of CCL2 on neurogenesis has not beenascertained. Here, to define neurogenic effects of CCL2 in NP-C, we applied humanrecombinant CCL2 to neural stem cells (NSCs) derived from NP-C mice. CCL2-treated NSCsshowed significantly increased capacity for self-renewal, proliferation and neuronaldifferentiation. Similar results were observed in the subventricular zone of NP-C miceafter CCL2 treatment. Furthermore, infusion of CCL2 into the NP-C mouse brain resulted inreduction of neuroinflammation. Taken together, our results demonstrate that CCL2 is apotential new therapeutic agent for NP-C. |
