The study was to investigate whether immunoproteasome (i-proteasome) and its downstream pathway are related to the pathogenesis of Parkinson’s disease (PD). Rats were treated with rotenone showed significant weight loss and dyskinesia, which is consistent with the degeneration of TH-positive neurons and the activation of Iba-1-positive microglia/macrophages. Two major catalytic subunits of i-proteasome (PSMB9 and PSMB8) were seldom expressed in rat substantia nigra (SN) under normal condition, but they were significantly up-regulated with the release of TNF-α and IFN-γ after exposure to rotenone. In addition, compared with control group, the antigen presentation-related proteins antigen peptide transporter (TAP) 1, TAP2, major histocompatibility complex (MHC)-I and MHC-II levels were significantly up-regulated in rotenone group, which was in line with the accumulation of α-syn. These findings suggested that i-proteasome and antigen presentation pathways (related proteins) were upregulated by rotenone in a PD rat model.

该研究旨在调查免疫蛋白酶体（i-蛋白酶体）及其下游途径是否与帕金森氏病（PD）的发病机制有关。鱼藤酮治疗的大鼠表现出明显的体重减轻和运动障碍，这与TH阳性神经元的变性和Iba-1阳性小胶质细胞/巨噬细胞的激活相一致。正常条件下，大鼠黑质（SN）中很少表达i-蛋白酶体的两个主要催化亚基（PSMB9和PSMB8），但是在暴露于鱼藤酮后，TNF-α和IFN-γ的释放显着上调了它们。此外，鱼藤酮组的抗原呈递相关蛋白抗原肽转运蛋白（TAP）1，TAP2，主要组织相容性复合物（MHC）-I和MHC-II的水平与对照组相比明显升高，这与α-syn的积累一致。这些发现表明在PD大鼠模型中鱼藤酮上调了i-蛋白酶体和抗原呈递途径（相关蛋白）。