Shelkovnikova T A, Ustiugov A A, Kokhan V S, Tarasova T V, Medvedeva V K, Khritankova I V, Bachurin S O, Ninkina N N
Biomed Khim. 2014 May-Jun;60(3):354-63. doi: 10.18097/pbmc20146003354.
In the present study we have used a transgenic mice overexpressing an amyloidogenic protein, gamma-synuclein, in the nervous system to address the effect of dimebon on proteinopathy progression. Neuroprotective effect of chronic dimebon administration in these mice at organismal level was confirmed by the increased lifespan. Using histological and biochemical approaches we have demonstrated that dimebon reduced the number of amyloid inclusions in spinal cord of transgenic animals and decreased the content of ubiquitinated proteins in detergent-insoluble fractions. These effects are likely to occur at the level of aggregated protein species, since transgene expression was not altered. Thus, pathological protein aggregation serves as one of dimebon targets in neurodegeneration.
在本研究中，我们使用了在神经系统中过度表达淀粉样蛋白生成蛋白γ-突触核蛋白的转基因小鼠，以研究 dimebon 对蛋白病进展的影响。在这些小鼠中，长期给予 dimebon 在机体水平上的神经保护作用通过寿命延长得到证实。使用组织学和生化方法，我们证明 dimebon 减少了转基因动物脊髓中淀粉样包涵体的数量，并降低了去污剂不溶性组分中泛素化蛋白的含量。由于转基因表达未改变，这些作用可能发生在聚集蛋白物种水平。因此，病理性蛋白聚集是 dimebon 在神经退行性变中的作用靶点之一。
