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The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
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The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary...
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The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
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Complex microtubule structures are present in resting cells and in dividing cells. In resting cells, they are responsible for maintaining the cellular architecture, tracks for intracellular transport, positioning of organelles, assembly of cilia and flagella. They mediate the bipolar spindle assembly for chromosomal segregation and positioning of the cell division plate in dividing cells. The formation of microtubule complex structures depends on the cell type, cell stage, and cell function.
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结核性硬化综合体 结核性硬化综合体

Kellen Winden1, E Martina Bebin2, Shafali Jeste3

  • 1Department of Neurology, Rosamund Stone Zander and Hansjoerg Wyss Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

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概括
此摘要是机器生成的。

结核性硬化综合体 (TSC) 是一种罕见的遗传疾病. 拉帕洛格治疗TSC表现,但TAND和耐火性仍然具有挑战性,突出显示了未满足的治疗需求.

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科学领域:

  • 遗传学 是一个遗传学.
  • 细胞生物学 细胞生物学
  • 神经学 神经学

背景情况:

  • 结核性硬化综合体 (TSC) 是一种罕见的遗传疾病,由TSC1或TSC2变体引起.
  • 它导致多个器官的良性瘤 (瘤) 和严重的神经问题,如和TAND.
  • 该TSC1/TSC2复合体调节mTOR信号通路,这是TSC病变发生的关键因素.

研究的目的:

  • 审查目前对TSC病变的理解.
  • 讨论TSC的临床管理,专注于mTOR抑制剂.
  • 确定TSC治疗的未满足需求,特别是TAND和耐火性.

主要方法:

  • 关于TSC病原和治疗的文献综述.
  • 分析TSC1/TSC2-mTOR通路的作用.
  • 评估当前的治疗策略及其局限性.

主要成果:

  • 拉帕米辛及其类似物 (拉帕洛格) 对包括瘤和发作在内的多种TSC表现有效.
  • 这些治疗向mTOR通路,在TSC中至关重要.
  • 尽管取得了进展,但在治疗TSC相关的神经精神疾病 (TAND) 和耐火性方面仍然存在重大挑战.

结论:

  • 该TSC1/TSC2-mTOR通路是TSC的核心,也是拉帕洛格治疗的目标.
  • 对于特定的TSC症状,已有批准的Rapalogue治疗方法.
  • 在TSC患者中仍然需要有效的TAND和耐火性治疗方法.