Novel targets to arrest neurodegeneration in several dementing conditions involving misfolded protein accumulations may be found in the diverse signaling pathways of the Mammalian/mechanistic target of rapamycin (mTOR). As a nutrient sensor, mTOR has important homeostatic functions to regulate energy metabolism and support neuronal growth and plasticity. However, in Alzheimer’s disease (AD), mTOR alternately plays important pathogenic roles by inhibiting both insulin signaling and autophagic removal of β-amyloid (Aβ) and phospho-tau (ptau) aggregates. It also plays a role in the cerebrovascular dysfunction of AD. mTOR is a serine/threonine kinase residing at the core in either of two multiprotein complexes termed mTORC1 and mTORC2. Recent data suggest that their balanced actions also have implications for Parkinson's disease (PD) and Huntington's disease (HD), Frontotemporal dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS). Beyond rapamycin; an mTOR inhibitor, there are rapalogs having greater tolerability and micro delivery modes, that hold promise in arresting these age dependent conditions.

中文翻译：

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雷帕霉素 (mTOR) 复合物在神经退行性变中的哺乳动物/机械靶点

在涉及错误折叠的蛋白质积累的几种痴呆条件下，可以在雷帕霉素的哺乳动物/机械靶标 (mTOR) 的不同信号通路中找到新的靶点来阻止神经退行性变。作为一种营养传感器，mTOR 具有调节能量代谢和支持神经元生长和可塑性的重要稳态功能。然而，在阿尔茨海默病 (AD) 中，mTOR 通过抑制胰岛素信号传导和 β-淀粉样蛋白 (Aβ) 和磷酸化 tau (ptau) 聚集体的自噬去除交替发挥重要的致病作用。它还在AD的脑血管功能障碍中起作用。mTOR 是一种丝氨酸/苏氨酸激酶，位于称为 mTORC1 和 mTORC2 的两种多蛋白复合物的核心。最近的数据表明，他们的平衡行为也对帕金森氏症有影响 s 病 (PD) 和亨廷顿病 (HD)、额颞叶痴呆 (FTD) 和肌萎缩侧索硬化症 (ALS)。超越雷帕霉素；作为 mTOR 抑制剂，rapalogs 具有更高的耐受性和微递送模式，有望阻止这些年龄依赖性病症。