Traina Giovanna, Federighi Giuseppe, Brunelli Marcello
Department of Internal Medicine, University of Perugia, Via S. Costanzo, Perugia 06126, Italy.
Neurochem Int. 2008 Dec;53(6-8):244-7. doi: 10.1016/j.neuint.2008.08.001. Epub 2008 Aug 7.
We investigated the effects of acetyl-l-carnitine on gene expression by means of the suppression subtractive hybridization method. The approach gives the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts after treatment of rats with acetyl-l-carnitine for 21 days. We observed that acetyl-l-carnitine increases the light-chain subunit of kinesin-1 gene expression. Recent evidences reported a link between kinesin-1 light-chain and Alzheimer's disease. Pathological hallmarks of Alzheimer's disease are potentially linked to alterations of the axonal compartments. Amyloid-beta peptide is a principal component of senile plaques and is considered to be central in the pathogenesis of the disease. The fast anterograde axonal transport of amyloid-beta peptide is mediated by direct binding to the light-chain subunit of kinesin-1. In this scenario, our results are of relevant importance for possible therapeutic intervention, suggesting a pathway for the treatment of Alzheimer's disease.
我们通过抑制性消减杂交法研究了乙酰左旋肉碱对基因表达的影响。该方法可生成消减cDNA文库，并在大鼠经乙酰左旋肉碱处理21天后鉴定差异表达的转录本。我们观察到乙酰左旋肉碱增加了驱动蛋白-1基因表达的轻链亚基。最近的证据报道了驱动蛋白-1轻链与阿尔茨海默病之间的联系。阿尔茨海默病的病理特征可能与轴突区室的改变有关。淀粉样β肽是老年斑的主要成分，被认为在该疾病的发病机制中起核心作用。淀粉样β肽的快速顺向轴突运输是通过与驱动蛋白-1的轻链亚基直接结合介导的。在这种情况下，我们的结果对于可能的治疗干预具有重要意义，为阿尔茨海默病的治疗提供了一条途径。
