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Multiplication of the SNCA locus exacerbates neuronal nuclear aging.

Publication ,  Journal Article
Tagliafierro, L; Zamora, ME; Chiba-Falek, O
Published in: Hum Mol Genet
February 1, 2019

Human-induced Pluripotent Stem Cell (hiPSC)-derived models have advanced the study of neurodegenerative diseases, including Parkinson's disease (PD). While age is the strongest risk factor for these disorders, hiPSC-derived models represent rejuvenated neurons. We developed hiPSC-derived Aged dopaminergic and cholinergic neurons to model PD and related synucleinopathies. Our new method induces aging through a `semi-natural' process, by passaging multiple times at the Neural Precursor Cell stage, prior to final differentiation. Characterization of isogenic hiPSC-derived neurons using heterochromatin and nuclear envelope markers, as well as DNA damage and global DNA methylation, validated our age-inducing method. Next, we compared neurons derived from a patient with SNCA-triplication (SNCA-Tri) and a Control. The SNCA-Tri neurons displayed exacerbated nuclear aging, showing advanced aging signatures already at the Juvenile stage. Noteworthy, the Aged SNCA-Tri neurons showed more α-synuclein aggregates per cell versus the Juvenile. We suggest a link between the effects of aging and SNCA overexpression on neuronal nuclear architecture.

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Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

February 1, 2019

Volume

28

Issue

3

Start / End Page

407 / 421

Location

England

Related Subject Headings

  • alpha-Synuclein
  • Parkinson Disease
  • Neurons
  • Induced Pluripotent Stem Cells
  • Humans
  • Genetics & Heredity
  • Dopaminergic Neurons
  • DNA Methylation
  • DNA Damage
  • Cholinergic Neurons
 

Citation

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Tagliafierro, L., Zamora, M. E., & Chiba-Falek, O. (2019). Multiplication of the SNCA locus exacerbates neuronal nuclear aging. Hum Mol Genet, 28(3), 407–421. https://doi.org/10.1093/hmg/ddy355
Tagliafierro, Lidia, Madison Elena Zamora, and Ornit Chiba-Falek. “Multiplication of the SNCA locus exacerbates neuronal nuclear aging.Hum Mol Genet 28, no. 3 (February 1, 2019): 407–21. https://doi.org/10.1093/hmg/ddy355.
Tagliafierro L, Zamora ME, Chiba-Falek O. Multiplication of the SNCA locus exacerbates neuronal nuclear aging. Hum Mol Genet. 2019 Feb 1;28(3):407–21.
Tagliafierro, Lidia, et al. “Multiplication of the SNCA locus exacerbates neuronal nuclear aging.Hum Mol Genet, vol. 28, no. 3, Feb. 2019, pp. 407–21. Pubmed, doi:10.1093/hmg/ddy355.
Tagliafierro L, Zamora ME, Chiba-Falek O. Multiplication of the SNCA locus exacerbates neuronal nuclear aging. Hum Mol Genet. 2019 Feb 1;28(3):407–421.
Journal cover image

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

February 1, 2019

Volume

28

Issue

3

Start / End Page

407 / 421

Location

England

Related Subject Headings

  • alpha-Synuclein
  • Parkinson Disease
  • Neurons
  • Induced Pluripotent Stem Cells
  • Humans
  • Genetics & Heredity
  • Dopaminergic Neurons
  • DNA Methylation
  • DNA Damage
  • Cholinergic Neurons