Yamamoto Shoji, Fukae Jiro, Mori Hideo, Mizuno Yoshikuni, Hattori Nobutaka
Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Tokyo 113-8421, Japan.
Neurosci Lett. 2006 Apr 3;396(3):187-91. doi: 10.1016/j.neulet.2005.11.068. Epub 2005 Dec 28.
Vesicular monoamine transporter 2 (VMAT2) is responsible for packing dopamine into vesicles, and reduces the effects of neurotoxins by sequestering them into vesicles. In this report, we tested the hypothesis that VMAT2 is associated with Lewy body (LB) formation by immunohistochemical staining of midbrain and cortical sections of autopsied brains of patients with Parkinson's disease (PD) and diffuse Lewy body disease (DLBD) for VMAT2 using a polyclonal antibody against VMAT2. LBs in the substantia nigra (SN) of PD and DLBD were immunoreactive for VMAT2, especially in the peripheral zone. Previous electron microscopic studies also revealed the presence of numerous dense core vesicles around the LBs, suggesting that these vesicles are related to LB formation. Indeed, the presence of a few vesicle-linked proteins such as synaptophysin and chromogranin A in LBs has been reported. Together with the low expression of VMAT2 in the SN of PD, the involvement of VMAT2 in LBs of the SN suggests the association of this protein in the neurodegeneration of nigral neurons in PD.
囊泡单胺转运体2(VMAT2)负责将多巴胺包装到囊泡中,并通过将神经毒素隔离到囊泡中来降低其作用。在本报告中,我们通过使用抗VMAT2的多克隆抗体对帕金森病(PD)和弥漫性路易体病(DLBD)患者尸检脑的中脑和皮质切片进行VMAT2免疫组织化学染色,来检验VMAT2与路易体(LB)形成相关的假说。PD和DLBD患者黑质(SN)中的LB对VMAT2呈免疫反应性,尤其是在外周区域。先前的电子显微镜研究还揭示了LB周围存在大量致密核心囊泡,表明这些囊泡与LB形成有关。事实上,已有报道称LB中存在一些与囊泡相关的蛋白质,如突触素和嗜铬粒蛋白A。连同PD患者SN中VMAT2的低表达,VMAT2参与SN中的LB提示该蛋白与PD中黑质神经元的神经变性有关。