Regulated endocrine-specific protein, 18 kDa (RESP18) was first cloned in 1994. Its function in the brain especially in neurodegenerative diseases remains unclear. In this study, RESP18 knockout (KO) and littermate wild-type (WT) mice were comprehensively analyzed. The dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was applied to generate subchronic Parkinson's disease model. We found that KO mice displayed a reduction in locomotor activity and motor coordination under physiological conditions. Five and six days after MPTP administration, the behavioral impairments were detected in MPTP-treated WT mice, whereas such impairments were not detected in MPTP-treated KO mice. The depletion of tyrosine hydroxylase-positive nerve fibers in the striatum was similar between MPTP-treated KO mice and WT littermates. Furthermore, the striatal level of α-synuclein protein was increased by treatment with MPTP in WT mice, but not in KO mice. The loss of dopaminergic neurons was markedly alleviated, and the activation of glial cells was inhibited in the substantia nigra of KO mice challenged with MPTP. These results suggested that RESP18 deficiency might protect dopaminergic neurons against MPTP toxicity.

受调节的内分泌特异性蛋白18 kDa（RESP18）于1994年首次克隆。其在大脑中的功能，特别是在神经退行性疾病中的功能尚不清楚。在本研究中，RESP18全面分析了基因敲除（KO）和同窝野生型（WT）小鼠。应用多巴胺能毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）生成亚慢性帕金森氏病模型。我们发现，KO小鼠在生理条件下显示出自发活动和运动协调性降低。在施用MPTP后五天和六天，在MPTP治疗的WT小鼠中检测到了行为障碍，而在MPTP治疗的KO小鼠中未检测到这种障碍。MPTP处理的KO小鼠和WT同窝仔小鼠中纹状体中酪氨酸羟化酶阳性神经纤维的消耗相似。此外，在WT小鼠中，通过MPTP治疗，α-突触核蛋白的纹状体水平增加了，但是在KO小鼠中没有。多巴胺能神经元的丧失得到明显缓解，MPTP攻击的KO小鼠黑质中神经胶质细胞的激活受到抑制。这些结果表明，RESP18缺乏可能保护多巴胺能神经元免受MPTP毒性。