据国外媒体报道，雷帕霉素是一种维持移植器官免疫能力的药物，然而科学家近期发现它另外一种用途：可用于治疗阿尔茨海默症(老年性痴呆)。令他们颇感兴趣的是，雷帕霉素的主要成分也存在于复活岛隔离土壤中的细菌产物，最新实验表明该物质施用在实验老鼠患体上可起到恢复识记缺陷能力。这一研究现发表在《生物化学杂志》( Journal of Biological Chemistry，JBC)上。
美国德克萨斯州大学健康科学中心生理部门副教授塞尔瓦托·奥多博士称，这是首次证实雷帕霉素能够对动物实验体恢复阿尔茨海默症相应症状的缺陷。奥多带领的研究小组发现雷帕霉素还可以降低实验老鼠体大脑组织的损害，这种损害状况与人类阿尔茨海默症患者大脑损伤十分相近。
奥多说：“我们的这项研究对于临床治疗具有重要深远意义。因为它是美国食品及药物管理局(FDA)审批的药物，估计在很短时间内能用于阿尔茨海默症临床性治疗。”2009年，来自三个研究机构的科学家曾宣称，雷帕霉素在老鼠抗衰老实验中可延长寿命，它是第一种干预性制药方法用于延长衰老动物的寿命。
研究小组对阿尔茨海默症老鼠患体喂养含有雷帕霉素的食物10个星期，最初实验老鼠的年龄为6个月，对应于年轻成年阶段，但它已出现记忆能力下降和大脑组织损害的症状。在实验的10周末，老鼠实验体在叫做“莫里斯水迷宫”的测试装置中进行测试，这种装置是一种小型游泳池，可用于评估老鼠等啮齿类动物的识记和记忆水平。在行为测试末期，对老鼠大脑分析显示雷帕霉素对于阿尔茨海默症具有损伤缓解作用。
在南太平洋的复活岛相对隔离的土壤环境中，一种细菌分泌的物质是雷帕霉素的主要成分，此前该物质也用于癌症研究测试。奥多说：“尽管当前我们还不清楚阿尔茨海默症患者也会呈现类似实验老鼠的治疗效果。但我们认为它将成为一种新型治疗阿尔茨海默症的治疗介入法。”(生物谷Bioon.com)
生物谷推荐原文出处：
JBC doi: 10.1074/jbc.M109.031278
Rapamycin Rescues TDP-43 Mislocalization and the Associated Low Molecular Mass Neurofilament Instability
Antonella Caccamo, Smita Majumder, Janice J. Deng, Yidong Bai, Fiona B. Thornton and Salvatore Oddo？,1
TDP-43 is a nuclear protein involved in exon skipping and alternative splicing. Recently, TDP-43 has been identified as the pathological signature protein in frontotemporal lobar degeneration with ubiquitin-positive inclusions and in amyotrophic lateral sclerosis. In addition, TDP-43-positive inclusions are present in Parkinson disease, dementia with Lewy bodies, and 30% of Alzheimer disease cases. Pathological TDP-43 is redistributed from the nucleus to the cytoplasm, where it accumulates. An ～25-kDa C-terminal fragment of TDP-43 accumulates in affected brain regions, suggesting that it may be involved in the disease pathogenesis. Here, we show that overexpression of the 25-kDa C-terminal fragment is sufficient to cause the mislocalization and cytoplasmic accumulation of endogenous full-length TDP-43 in two different cell lines, thus recapitulating a key biochemical characteristic of TDP-43 proteinopathies. We also found that TDP-43 mislocalization is associated with a reduction in the low molecular mass neurofilament mRNA levels. Notably, we show that the autophagic system plays a role in TDP-43 metabolism. Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. Our results suggest that autophagy induction may be a valid therapeutic target for TDP-43 proteinopathies.
