Narita M, Bu G, Holtzman D M, Schwartz A L
Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Neurochem. 1997 Feb;68(2):587-95. doi: 10.1046/j.1471-4159.1997.68020587.x.
The epsilon 4 allele of apolipoprotein E (apoE) is an important risk factor for Alzheimer's disease. A major neuronal receptor for apoE within the brain is the low-density lipoprotein receptor-related protein (LRP). Using primary cultured hippocampal neurons, we examined the role of LRP in early neuronal development. LRP, as well as a 39-kDa protein that regulates its activity, is localized abundantly in developing neurons. Both the 39-kDa protein and an anti-LRP antibody inhibited neurite outgrowth of primary hippocampal neurons cultured in either serum-containing medium or on cortical astrocyte monolayers in serum-free medium. It is noteworthy that microtubule-associated protein-2 immunoreactive process outgrowth was decreased significantly in hippocampal neurons cultured on cortical astrocytes derived from apoE-deficient mice and was not diminished further following incubation with LRP inhibitors. Thus, these results suggest that LRP can influence aspects of neuronal process development and that apoE-containing lipoproteins may be one of the major LRP ligands that can contribute to this process.
载脂蛋白E（apoE）的ε4等位基因是阿尔茨海默病的一个重要风险因素。大脑中apoE的主要神经元受体是低密度脂蛋白受体相关蛋白（LRP）。我们使用原代培养的海马神经元，研究了LRP在早期神经元发育中的作用。LRP以及一种调节其活性的39 kDa蛋白，在发育中的神经元中大量定位。39 kDa蛋白和抗LRP抗体均抑制了在含血清培养基中培养的原代海马神经元的神经突生长，也抑制了在无血清培养基中皮质星形胶质细胞单层上培养的原代海马神经元的神经突生长。值得注意的是，在源自载脂蛋白E缺陷小鼠的皮质星形胶质细胞上培养的海马神经元中，微管相关蛋白-2免疫反应性突起生长显著减少，并且在用LRP抑制剂孵育后没有进一步减少。因此，这些结果表明LRP可以影响神经元突起发育的各个方面，并且含apoE的脂蛋白可能是有助于这一过程的主要LRP配体之一。
