Department of Neurology, The Affiliated Suzhou Science & Technology Town Hospital of Nanjing Medical University, Suzhou, China.
Department of Neurology, The Affiliated Suzhou Science & Technology Town Hospital of Nanjing Medical University, Suzhou, China; Department of Neurology, Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, China.
J Clin Neurosci. 2022 Feb;96:154-162. doi: 10.1016/j.jocn.2021.11.002. Epub 2021 Nov 19.
The dynein protein plays a key role in the degradation pathway by attaching to targeted molecules and transporting the autophagosome to the centrosome. Aging plays an important role in the pathogenesis of Parkinson's disease (PD), but its effect on dynein is not clear. In this study we analyzed behavioral characteristics using the rod endurance test and climbing rod time test in different aged mice (3 months, 12 months, 20 months), and measured protein expression of dynein, α-synuclein, Tctex-1, and LC3 in the substantianigra of the mice by Western blot. The mRNA levels of dynein, α-synuclein, LC3 and Tctex-1 were measured by quantitative real time reverse transcription PCR, and detecting expression of dynein and α-synuclein by immunofluorescence. We found the motor functions of A53T mutant mice, in 12 months and 20 months, decreased more significantly compared with normal mice (p < 0.05). In addition, the expression of dynein, LC3-Ⅱ and Tctex-1 proteins in the substantia nigra of the two groups decreased with age. However, α-synuclein protein increased gradually with age, with significantly higher levels in the PD groups compared with age matched controls (p < 0.05). These results were confirmed by immunofluorescence. Our data demonstrates that dynein and other autophagy proteins change with age, and this is associated with increased α-synuclein. Therefore, therapeutics that prevent dynein dysfunction may offer novel treatments for PD and other autophagy related diseases.
动力蛋白蛋白通过附着在靶分子上并将自噬体运送到中心体，在降解途径中发挥关键作用。衰老在帕金森病（PD）的发病机制中起着重要作用，但它对动力蛋白的影响尚不清楚。在这项研究中，我们使用不同年龄的小鼠（3 个月、12 个月、20 个月）的棒耐力试验和爬杆时间试验分析了行为特征，并通过 Western blot 测定了小鼠黑质中动力蛋白、α-突触核蛋白、Tctex-1 和 LC3 的蛋白表达。通过定量实时逆转录 PCR 测量动力蛋白、α-突触核蛋白、LC3 和 Tctex-1 的 mRNA 水平，并通过免疫荧光检测动力蛋白和α-突触核蛋白的表达。我们发现 A53T 突变小鼠的运动功能在 12 个月和 20 个月时比正常小鼠下降更为明显（p<0.05）。此外，两组黑质中动力蛋白、LC3-Ⅱ和 Tctex-1 蛋白的表达随年龄增长而降低。然而，α-突触核蛋白蛋白随年龄逐渐增加，PD 组与年龄匹配的对照组相比水平显著升高（p<0.05）。免疫荧光也证实了这些结果。我们的数据表明，动力蛋白和其他自噬蛋白随年龄变化，这与α-突触核蛋白的增加有关。因此，预防动力蛋白功能障碍的治疗方法可能为 PD 和其他自噬相关疾病提供新的治疗方法。
