老年痴呆症已经成为一个世界性难题
近日，韩国一研究小组首次发现了制造毒性物质诱发阿尔茨海默病（老年痴呆症）的基因。
韩国国立保健研究院生命医学中心的高永浩（音）博士研究小组说，发现一种叫“SUMO1”的蛋白质诱导生成引发老年痴呆症的毒性物质。老年痴呆症因毒性物质(Beta-Amyloid Peptide)在大脑里积累而发生，因此次发现找到了可抑制毒性物质在脑里生成的一种线索。
该研究小组说，此次研究为今后研发老年性痴呆症治疗剂提供了科学根据。该研究小组从致使引发痴呆症的实验用老鼠的脑组织中发现一种叫SUMO1的蛋白质在增加，并弄清该蛋白质促进毒性物质的生成。该研究结果计划在国际衰老研究界的著名学术杂志《衰老神经生物学(Neurobiology of Aging)》上发表。
韩国有46.1万名老年痴呆症患者。但还没有有效治疗剂，而且还没有弄清诱发老年痴呆症的基因难以进行有效的预防。
国立保健研究员相关人士说：“患老年痴呆症的病例占国内痴呆病例的70%左右。计划以这次研究成果为基础，继续研发预防和缓解痴呆症的技术。”
SUMO1 modulates Aβ generation via BACE1 accumulation
Sang-Moon Yun, Sun-Jung Cho, Jae Chun Song, Sung Yeon Song, Sangmee Ahn Jo, Chulman Jo, Keejung Yoon, Rudolph E. Tanzi, Eui-Ju Choi, Young Ho Koh
Accumulation of disease-related proteins is a characteristic event observed in the pathogenesis of neurodegenerative diseases. β-secretase (BACE)-1, which initiates generation of β-amyloid (Aβ), is increased in the Alzheimer's diseased brain. However, the mechanisms of BACE1 accumulation in Alzheimer's disease are largely unknown. In this report, we found that small ubiquitin-like modifier (SUMO)-1 interacts with the dileucine motif of BACE1 and regulates the level of BACE1 protein. This was proved by the coimmunoprecipitation, and gain or loss of function experiments. Altering 3 SUMO isoforms affects BACE1 protein levels, and consequently results in altered amyloid precursor protein processing and Aβ generation. BACE1 levels were increased in response to Aβ or apoptosis, but not in cells lacking SUMO1. Aβ increased SUMO1 protein levels in rat cortical neurons. Moreover, SUMO1 immunoreactivity was increased in the amyloid precursor protein transgenic mice. Furthermore, the C-terminus fragments of BACE1 containing dileucine motif reduced Aβ generation by SUMO1 overexpression. Our study indicates SUMO1 is not only a novel and potent regulator of BACE1 accumulation and Aβ generation but also a potential therapeutic target for Alzheimer's disease.
