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

Publication ,  Journal Article
Tagliafierro, L; Glenn, O-C; Zamora, ME; Beach, TG; Woltjer, RL; Lutz, MW; Chiba-Falek, O
Published in: Alzheimers Dement
November 2017

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.

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Published In

Alzheimers Dement

DOI

EISSN

1552-5279

Publication Date

November 2017

Volume

13

Issue

11

Start / End Page

1237 / 1250

Location

United States

Related Subject Headings

  • alpha-Synuclein
  • Stem Cells
  • RNA, Messenger
  • Polymorphism, Single Nucleotide
  • Parkinson Disease
  • Neurons
  • Nerve Tissue Proteins
  • MicroRNAs
  • Male
  • Lewy Body Disease
 

Citation

APA
Chicago
ICMJE
MLA
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Tagliafierro, L., Glenn, O.-C., Zamora, M. E., Beach, T. G., Woltjer, R. L., Lutz, M. W., & Chiba-Falek, O. (2017). Genetic analysis of α-synuclein 3' untranslated region and its corresponding microRNAs in relation to Parkinson's disease compared to dementia with Lewy bodies. Alzheimers Dement, 13(11), 1237–1250. https://doi.org/10.1016/j.jalz.2017.03.001
Tagliafierro, Lidia, Omolara-Chinue Glenn, Madison E. Zamora, Thomas G. Beach, Randy L. Woltjer, Michael W. Lutz, and Ornit Chiba-Falek. “Genetic analysis of α-synuclein 3' untranslated region and its corresponding microRNAs in relation to Parkinson's disease compared to dementia with Lewy bodies.Alzheimers Dement 13, no. 11 (November 2017): 1237–50. https://doi.org/10.1016/j.jalz.2017.03.001.
Tagliafierro L, Glenn O-C, Zamora ME, Beach TG, Woltjer RL, Lutz MW, et al. Genetic analysis of α-synuclein 3' untranslated region and its corresponding microRNAs in relation to Parkinson's disease compared to dementia with Lewy bodies. Alzheimers Dement. 2017 Nov;13(11):1237–50.
Tagliafierro, Lidia, et al. “Genetic analysis of α-synuclein 3' untranslated region and its corresponding microRNAs in relation to Parkinson's disease compared to dementia with Lewy bodies.Alzheimers Dement, vol. 13, no. 11, Nov. 2017, pp. 1237–50. Pubmed, doi:10.1016/j.jalz.2017.03.001.
Tagliafierro L, Glenn O-C, Zamora ME, Beach TG, Woltjer RL, Lutz MW, Chiba-Falek O. Genetic analysis of α-synuclein 3' untranslated region and its corresponding microRNAs in relation to Parkinson's disease compared to dementia with Lewy bodies. Alzheimers Dement. 2017 Nov;13(11):1237–1250.
Journal cover image

Published In

Alzheimers Dement

DOI

EISSN

1552-5279

Publication Date

November 2017

Volume

13

Issue

11

Start / End Page

1237 / 1250

Location

United States

Related Subject Headings

  • alpha-Synuclein
  • Stem Cells
  • RNA, Messenger
  • Polymorphism, Single Nucleotide
  • Parkinson Disease
  • Neurons
  • Nerve Tissue Proteins
  • MicroRNAs
  • Male
  • Lewy Body Disease