Outeiro Tiago Fleming, Marques Oldriska, Kazantsev Aleksey
Cellular and Molecular Neuroscience Unit, Instituto de Medicina Molecular, Instituto de Fisiologia, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.
Biochim Biophys Acta. 2008 Jun;1782(6):363-9. doi: 10.1016/j.bbadis.2008.02.010. Epub 2008 Mar 7.
The sirtuins are a family of enzymes which control diverse and vital cellular functions, including metabolism and aging. Manipulations of sirtuin activities cause activation of anti-apoptotic, anti-inflammatory, anti-stress responses, and the modulation of an aggregation of proteins involved in neurodegenerative disorders. Recently, sirtuins were found to be disease-modifiers in various models of neurodegeneration. However, almost in all instances, the exact mechanisms of neuroprotection remain elusive. Nevertheless, the manipulation of sirtuin activities is appealing as a novel therapeutic strategy for the treatment of currently fatal human disorders such as Alzheimer's and Parkinson's diseases. Here, we review current data which support the putative therapeutic roles of sirtuin in aging and in neurodegenerative diseases and the feasibility of the development of sirtuin-based therapies.
沉默调节蛋白是一类控制多种重要细胞功能的酶,包括新陈代谢和衰老。对沉默调节蛋白活性的调控会引发抗凋亡、抗炎、抗应激反应,并调节参与神经退行性疾病的蛋白质聚集。最近,在各种神经退行性变模型中发现沉默调节蛋白是疾病修饰因子。然而,几乎在所有情况下,神经保护的确切机制仍然难以捉摸。尽管如此,作为治疗目前致命的人类疾病如阿尔茨海默病和帕金森病的一种新的治疗策略,对沉默调节蛋白活性的调控很有吸引力。在此,我们综述了支持沉默调节蛋白在衰老和神经退行性疾病中假定治疗作用的当前数据,以及基于沉默调节蛋白的疗法开发的可行性。