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协调者c-regulatory元素 (cCREs) 链接代谢和阿尔茨海默氏病 (AD) 风险在下丘脑. 这些新元素调节多个基因,为AD提供了新的治疗点.

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科学领域:

  • 基因组学和表观遗传学
  • 神经科学是一个神经科学.
  • 代谢研究研究 代谢研究

背景情况:

  • 阿尔茨海默病 (AD) 是导致死亡的主要原因,40%的风险是可改变的,特别是通过代谢因素.
  • 代谢途径通过cis调节元件 (CREs) 影响基因表达,但将代谢与AD联系起来的机制尚不清楚.
  • 一个新的CREs类,协调CREs (cCREs),与单个CREs (sCREs) 不同,同时调节多个基因.

研究的目的:

  • 研究cCREs在将代谢因素与下丘脑组织中的阿尔茨海默病 (AD) 联系中的作用.
  • 探索cCREs如何在对代谢变化的反应中调解基因共同表达.
  • 为了确定与AD风险相关的cCREs中的潜在治疗点.

主要方法:

  • PLAC-Seq被用来绘制3D染色质结构和活跃的cis-regulatory接触在不同代谢状态的小鼠下丘脑.
  • 在C57BL/6和5xFAD小鼠模型上进行了大量RNA测序和单核多组 (GEX和ATAC) 测序.
  • 分析的重点是识别cCREs及其与基因共同表达和AD风险基因的关联.

主要成果:

  • 协调器调节元件 (cCREs) 在小鼠下丘脑中占CREs的18%.
  • 通过"相互排斥"或"共同表达"模型,cCREs促进基因共同表达,以应对代谢变化.
  • 阿兹海默氏症风险基因与cCREs具有显著的促进者接触,表明它们在调解阿兹海默氏症病理的代谢联系方面的作用.

结论:

  • 一种涉及下丘脑cCREs的新型基因调节机制将新陈代谢与AD风险联系起来.
  • 这些发现提供了关于代谢因素如何影响AD进展和性的关键见解.
  • 在AD风险位置内的cCREs代表了阿尔茨海默病的潜在治疗点.