Novel insights into the role of circular RNAs in Parkinson disease: An emerging renaissance in the management of neurodegenerative diseases

J Neurosci Res. 2022 Sep;100(9):1775-1790. doi: 10.1002/jnr.25094. Epub 2022 May 31.


Parkinson's disease (PD), as a debilitating neurodegenerative disease, particularly affects the elderly population, and is clinically identified by resting tremor, rigidity, and bradykinesia. Pathophysiologically, PD is characterized by an early loss of dopaminergic neurons in the Substantia nigra pars compacta, accompanied by the extensive aggregation of alpha-synuclein (α-Syn) in the form of Lewy bodies. The onset of PD has been reported to be influenced by multiple biological molecules. In this context, circular RNAs (circRNAs), as tissue-specific noncoding RNAs with closed structures, have been recently demonstrated to involve in a set of PD's pathogenic processes. These RNA molecules can either up- or downregulate the expression of α-Syn, as well as moderating its accumulation through different regulatory mechanisms, in which targeting microRNAs (miRNAs) is considered the most common pathway. Since circRNAs have prominent structural and biological characteristics, they could also be considered as promising candidates for PD diagnosis and treatment. Unfortunately, PD has become a global health concern, and a large number of its pathogenic processes are still unclear; thus, it is crucial to elucidate the ambiguous aspects of PD pathophysiology to improve the efficiency of diagnostic and therapeutic strategies. In line with this fact, the current review aims to highlight the interplay between circRNAs and PD pathogenesis, and then discusses the diagnostic and therapeutic potential of circRNAs in PD progression. This study will thus be the first of its kind reviewing the relationship between circRNAs and PD.

Keywords: Parkinson disease; alpha-synuclein; circRNAs; dopaminergic neurons; neurodegenerative diseases.

Publication types

  • Review

MeSH terms

  • Aged
  • Dopaminergic Neurons / metabolism
  • Humans
  • MicroRNAs* / genetics
  • Neurodegenerative Diseases* / pathology
  • Parkinson Disease* / genetics
  • Parkinson Disease* / metabolism
  • Parkinson Disease* / therapy
  • RNA, Circular / genetics
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism


  • MicroRNAs
  • RNA, Circular
  • alpha-Synuclein