Detection of novel intracellular α-synuclein oligomeric species by fluorescence lifetime imaging

Jochen Klucken, Tiago F. Outeiro, Paul Nguyen, Pamela J McLean, Bradley T. Hyman

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Oligomerization and aggregation of α-synuclein molecules are believed to play a major role in neuronal dysfunction and loss in Parkinson's disease (PD) and dementia with Lewy bodies. However, α-synuclein oligomerization and aggregation have been detected only indirectly in cells using detergent extraction methods. Here, we show for the first time intracellular α-synuclein oligomerization using fluorescence lifetime imaging (FLIM). Two forms of α-synuclein homomeric interactions were detected: an antiparallel amino terminus-carboxyl terminus interaction between α-synuclein molecules, and a close amino terminus-carboxy terminus interaction within single α-synuclein molecules. Coexpression of the chaperone protein Hsp70, which can block α-synuclein toxicity in several systems, causes α-synuclein to adopt a different, open conformation, but Hsp70 does not alter α-synuclein-α-synuclein interactions. Thus, the neuroprotective effect of Hsp70 can be explained by its chaperone activity on α-synuclein molecules, rather than alteration of α-synuclein- α-synuclein interactions.

Original languageEnglish (US)
Pages (from-to)2050-2057
Number of pages8
JournalFASEB Journal
Volume20
Issue number12
DOIs
StatePublished - Oct 2006
Externally publishedYes

Fingerprint

Synucleins
Optical Imaging
Fluorescence
image analysis
fluorescence
Imaging techniques
neuroprotective effect
dementia
Parkinson disease
detergents
Oligomerization
toxicity
Molecules
oligomerization
proteins
Agglomeration
cells
Lewy Body Disease
methodology
Neuroprotective Agents

Keywords

  • Chaperone
  • Lewy body disease
  • Parkinson's disease
  • Protein aggregation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Detection of novel intracellular α-synuclein oligomeric species by fluorescence lifetime imaging. / Klucken, Jochen; Outeiro, Tiago F.; Nguyen, Paul; McLean, Pamela J; Hyman, Bradley T.

In: FASEB Journal, Vol. 20, No. 12, 10.2006, p. 2050-2057.

Research output: Contribution to journalArticle

Klucken, Jochen ; Outeiro, Tiago F. ; Nguyen, Paul ; McLean, Pamela J ; Hyman, Bradley T. / Detection of novel intracellular α-synuclein oligomeric species by fluorescence lifetime imaging. In: FASEB Journal. 2006 ; Vol. 20, No. 12. pp. 2050-2057.
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