Bimolecular Fluorescence Complementation of Alpha-synuclein Demonstrates its Oligomerization with Dopaminergic Phenotype in Mice

Waijiao Cai, Danielle Feng, Michael A. Schwarzschild, Pamela J McLean, Xiqun Chen

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Alpha-synuclein (αSyn) is encoded by the first causal gene identified in Parkinson's disease (PD) and is the main component of Lewy bodies, a pathological hallmark of PD. aSyn-based animal models have contributed to our understanding of PD pathophysiology and to the development of therapeutics. Overexpression of human wildtype αSyn by viral vectors in rodents recapitulates the loss of dopaminergic neurons from the substantia nigra, another defining pathological feature of the disease. The development of a rat model exhibiting bimolecular fluorescence complementation (BiFC) of αSyn by recombinant adeno-associated virus facilitates detection of the toxic αSyn oligomers species. We report here neurochemical, neuropathological and behavioral characterization of BiFC of αSyn in mice. Overexpression and oligomerization of αSyn through BiFC is detected by conjugated fluorescence. Reduced striatal dopamine and loss of nigral dopaminergic neurons are accompanied neuroinflammation and abnormal motor activities. Our mouse model may provide a valuable tool to study the role of αSyn in PD and to explore therapeutic approaches.

Original languageEnglish (US)
Pages (from-to)13-22
Number of pages10
JournalEBioMedicine
Volume29
DOIs
StatePublished - Mar 1 2018

Fingerprint

Synucleins
alpha-Synuclein
Oligomerization
Fluorescence
Phenotype
Parkinson Disease
Dopaminergic Neurons
Substantia Nigra
Neurons
Lewy Bodies
Corpus Striatum
Dependovirus
Poisons
Viruses
Oligomers
Rats
Rodentia
Dopamine
Animals
Motor Activity

Keywords

  • Alpha-synuclein
  • Mouse model
  • Neuroinflammation
  • Oligomers
  • Parkinson's disease

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Bimolecular Fluorescence Complementation of Alpha-synuclein Demonstrates its Oligomerization with Dopaminergic Phenotype in Mice. / Cai, Waijiao; Feng, Danielle; Schwarzschild, Michael A.; McLean, Pamela J; Chen, Xiqun.

In: EBioMedicine, Vol. 29, 01.03.2018, p. 13-22.

Research output: Contribution to journalArticle

Cai, Waijiao ; Feng, Danielle ; Schwarzschild, Michael A. ; McLean, Pamela J ; Chen, Xiqun. / Bimolecular Fluorescence Complementation of Alpha-synuclein Demonstrates its Oligomerization with Dopaminergic Phenotype in Mice. In: EBioMedicine. 2018 ; Vol. 29. pp. 13-22.
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