Genetic analysis of α-synuclein 3' untranslated region and its corresponding microRNAs in relation to Parkinson's disease compared to dementia with Lewy bodies.

Journal Article (Journal Article)

INTRODUCTION: The α-synuclein (SNCA) gene has been implicated in the etiology of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). METHODS: A computational analysis of SNCA 3' untranslated region to identify potential microRNA (miRNA) binding sites and quantitative real-time polymerase chain reaction (PCR) to determine their expression in isogenic induced pluripotent stem cell-derived dopaminergic and cholinergic neurons as a model of PD and DLB, respectively, were performed. In addition, we performed a deep sequencing analysis of the SNCA 3' untranslated region of autopsy-confirmed cases of PD, DLB, and normal controls, followed by genetic association analysis of the identified variants. RESULTS: We identified four miRNA binding sites and observed a neuronal-type-specific expression profile for each miRNA in the different isogenic induced pluripotent stem cell-derived dopaminergic and cholinergic neurons. Furthermore, we found that the short structural variant rs777296100-polyT was moderately associated with DLB but not with PD. DISCUSSION: We suggest that the regulation of SNCA expression through miRNAs is neuronal-type-specific and possibly plays a part in the phenotypic heterogeneity of synucleinopathies. Furthermore, genetic variability in the SNCA gene may contribute to synucleinopathies in a pathology-specific manner.

Full Text

Duke Authors

Cited Authors

  • Tagliafierro, L; Glenn, O-C; Zamora, ME; Beach, TG; Woltjer, RL; Lutz, MW; Chiba-Falek, O

Published Date

  • November 2017

Published In

Volume / Issue

  • 13 / 11

Start / End Page

  • 1237 - 1250

PubMed ID

  • 28431219

Pubmed Central ID

  • PMC5647200

Electronic International Standard Serial Number (EISSN)

  • 1552-5279

Digital Object Identifier (DOI)

  • 10.1016/j.jalz.2017.03.001


  • eng

Conference Location

  • United States