Role of circRNA in pathogenesis of Alzheimer ' s disease

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2022 Jul 28;47(7):960-966. doi: 10.11817/j.issn.1672-7347.2022.210729.
[Article in English, Chinese]

Abstract

Circular RNA (circRNA) is a covalently closed-loop non-coding RNA that exists widely in the transcriptome of eukaryotic cells. It participates in a variety of pathophysiological processes by acting as a microRNA sponge, regulating the level of protein transcription, and interacting with RNA binding proteins. CircRNA is enriched in the cortex, hippocampus, brain white matter, and photoreceptor neurons of aging bodies, and they can be used as a biomarker for neural senescence. The expression levels of circRNA in peripheral blood and synapses in Alzheimer's disease (AD) patients are increased, which are involved in the occurrence and prognosis of AD. Different circRNAs such as HDAC9, Homer1, Cwc27, Tulp4, and PTK2 can lead to AD pathological changes via increasing amyloid-β deposition, promoting tau protein hyperphosphorylation, aggravating neuroinflammation and mitochondrial dysfunction, which result in the cognitive decline.

环状RNA(circRNA)是普遍存在于真核细胞转录组中的共价闭环非编码RNA,其通过充当微RNA海绵、调节蛋白质转录水平、与RNA结合蛋白质作用等参与机体的多种病理、生理过程。CircRNA富集于衰老机体的皮层、海马体、大脑白质及光感受器神经元中,可作为神经衰老的生物标志物。CircRNA在阿尔茨海默病(Alzheimer’s disease,AD)患者外周血及神经突触中的表达水平增高,参与AD的发生与转归。不同的circRNA[如HDAC9、HOMER1、Cwc27、Tulp4、PTK2]可通过增加β-淀粉样蛋白沉积、促进tau蛋白过度磷酸化、加重神经炎症及引发线粒体功能障碍等导致患者出现AD病理改变,从而诱发认知功能下降。.

Keywords: Alzheimer’s disease; circular RNA; pathogenesis.

MeSH terms

  • Alzheimer Disease* / genetics
  • Amyloid beta-Peptides / metabolism
  • Cyclophilins / metabolism
  • Hippocampus / metabolism
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular / genetics

Substances

  • Amyloid beta-Peptides
  • MicroRNAs
  • RNA, Circular
  • Cwc27 protein, human
  • Cyclophilins