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Up-regulation of SNCA gene expression: implications to synucleinopathies.

Publication ,  Journal Article
Tagliafierro, L; Chiba-Falek, O
Published in: Neurogenetics
July 2016

Synucleinopathies are a group of neurodegenerative diseases that share a common pathological lesion of intracellular protein inclusions largely composed by aggregates of alpha-synuclein protein. Accumulating evidence, including genome wide association studies, has implicated alpha-synuclein (SNCA) gene in the etiology of synucleinopathies. However, the precise variants within SNCA gene that contribute to the sporadic forms of Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and other synucleinopathies and their molecular mechanisms of action remain elusive. It has been suggested that SNCA expression levels are critical for the development of these diseases. Here, we review several model systems that have been developed to advance the understanding of the role of SNCA expression levels in the etiology of synucleinopathies. We also describe different molecular mechanisms that regulate SNCA gene expression and discuss possible strategies for SNCA down-regulation as means for therapeutic approaches. Finally, we highlight some examples that underscore the relationships between the genetic association findings and the regulatory mechanisms of SNCA expression, which suggest that genetic variability in SNCA locus is directly responsible, at least in part, to the changes in gene expression and explain the reported associations of SNCA with synucleinopathies. Future studies utilizing induced pluripotent stem cells (iPSCs)-derived neuronal lines and genome editing by CRISPR/Cas9, will allow us to validate, characterize, and manipulate the effects of particular cis-genetic variants on SNCA expression. Moreover, this model system will enable us to compare different neuronal and glial lineages involved in synucleinopathies representing an attractive strategy to elucidate-common and specific-SNCA-genetic variants, regulatory mechanisms, and vulnerable expression levels underlying synucleinopathy spectrum disorders. This forthcoming knowledge will support the development of precision medicine for synucleinopathies.

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Published In

Neurogenetics

DOI

EISSN

1364-6753

Publication Date

July 2016

Volume

17

Issue

3

Start / End Page

145 / 157

Location

United States

Related Subject Headings

  • alpha-Synuclein
  • Up-Regulation
  • Protein Aggregation, Pathological
  • Parkinson Disease
  • Neurology & Neurosurgery
  • Multiple System Atrophy
  • Lewy Body Disease
  • Humans
  • Gene Expression Regulation
  • Gene Expression
 

Citation

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Chicago
ICMJE
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Tagliafierro, L., & Chiba-Falek, O. (2016). Up-regulation of SNCA gene expression: implications to synucleinopathies. Neurogenetics, 17(3), 145–157. https://doi.org/10.1007/s10048-016-0478-0
Tagliafierro, L., and O. Chiba-Falek. “Up-regulation of SNCA gene expression: implications to synucleinopathies.Neurogenetics 17, no. 3 (July 2016): 145–57. https://doi.org/10.1007/s10048-016-0478-0.
Tagliafierro L, Chiba-Falek O. Up-regulation of SNCA gene expression: implications to synucleinopathies. Neurogenetics. 2016 Jul;17(3):145–57.
Tagliafierro, L., and O. Chiba-Falek. “Up-regulation of SNCA gene expression: implications to synucleinopathies.Neurogenetics, vol. 17, no. 3, July 2016, pp. 145–57. Pubmed, doi:10.1007/s10048-016-0478-0.
Tagliafierro L, Chiba-Falek O. Up-regulation of SNCA gene expression: implications to synucleinopathies. Neurogenetics. 2016 Jul;17(3):145–157.
Journal cover image

Published In

Neurogenetics

DOI

EISSN

1364-6753

Publication Date

July 2016

Volume

17

Issue

3

Start / End Page

145 / 157

Location

United States

Related Subject Headings

  • alpha-Synuclein
  • Up-Regulation
  • Protein Aggregation, Pathological
  • Parkinson Disease
  • Neurology & Neurosurgery
  • Multiple System Atrophy
  • Lewy Body Disease
  • Humans
  • Gene Expression Regulation
  • Gene Expression