Identification of ApoE as an autocrine/paracrine factor that stimulates neural stem cell survival via MAPK/ERK signaling pathway

Neural Stem Cell Laboratory, Institute of Medical Biology, Singapore.
Journal of Neurochemistry (Impact Factor: 4.28). 02/2011; 117(3):565-78. DOI: 10.1111/j.1471-4159.2011.07227.x
Source: PubMed

ABSTRACT J. Neurochem. (2011) 117, 565–578.
Neural stem cells (NSCs) are self-renewing multipotent cells that undergo symmetric and asymmetric cell division during development of the nervous system. The behavior of NSCs is tightly regulated by intrinsic processes such as transcriptional and post-transcriptional control, as well as the stem cell niche factors that activate ligand-receptor-mediated signaling pathways. However, the role of these niche factors that regulate NSC behavior is not clearly understood. We identified chondroitin sulfate proteoglycan, apolipoprotein E (ApoE) and cystatin C as factors derived from the mouse neurosphere conditioned medium. Here, we show that ApoE is an autocrine/paracrine factor that regulates NSC survival. Stimulation of NSC survival is mediated by ApoE receptor interaction and the downstream extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway. In addition, ApoE also enhanced neurosphere formation of mouse embryonic stem cell-derived NSCs. Finally, in vitro differentiation studies with ApoE knock-out NSCs suggest a role for ApoE in oligodendrogenesis.

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Available from: Muly Tham, Nov 14, 2014
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    • "In addition to these neuronal effects, apoE plays a role in oligodendrogenesis [79] – a number of brain imaging studies show white-matter differences in carriers of different APOE isoforms [28]. Further research on apoE’s role in neurodevelopment and synaptic plasticity will be important in linking brain imaging and observational studies to underlying mechanisms, and to determine whether and which of apoE’s potential risk-inducing effects may in fact be congenital in nature. "
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