HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Klucken, J. Articles by Hyman, B. T. Search for Related Content PubMed PubMed Citation Articles by Klucken, J. Articles by Hyman, B. T.

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

Jochen Klucken^*,, Tiago F. Outeiro^*, Paul Nguyen^*, Pamela J. McLean^*,1 and Bradley T. Hyman^*

^* MassGeneral Institute for Neurodegenerative Disease, Alzheimer’s Disease Research Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA;

Department of Neurology, University of Regensburg, Regensburg, Germany

¹Correspondence: MassGeneral Institute for Neurodegenerative Disease, Alzheimer’s Disease Research Unit, Massachusetts General Hospital, 114 16^th St., Charlestown, MA 02129 USA. E-mail: pmclean{at}partners.org

Oligomerization and aggregation of -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, -synuclein oligomerization and aggregation have been detected only indirectly in cells using detergent extraction methods. Here, we show for the first time intracellular -synuclein oligomerization using fluorescence lifetime imaging (FLIM). Two forms of -synuclein homomeric interactions were detected: an antiparallel amino terminus-carboxyl terminus interaction between -synuclein molecules, and a close amino terminus-carboxy terminus interaction within single -synuclein molecules. Coexpression of the chaperone protein Hsp70, which can block -synuclein toxicity in several systems, causes -synuclein to adopt a different, open conformation, but Hsp70 does not alter -synuclein–-synuclein interactions. Thus, the neuroprotective effect of Hsp70 can be explained by its chaperone activity on -synuclein molecules, rather than alteration of -synuclein–-synuclein interactions.—Klucken, J., Outeiro, T. F., Nyugen, P., McLean, P. J., and Hyman, B. T. Detection of novel intracellular -synuclein oligomeric species by fluorescence lifetime imaging.

Key Words: Parkinson’s disease • Lewy body disease • chaperone • protein aggregation

This article has been cited by other articles:

				P. Jiang, L.-w. Ko, K. R. Jansen, T. E. Golde, and S.-H. Yen Using leucine zipper to facilitate {alpha}-synuclein assembly FASEB J, September 1, 2008; 22(9): 3165 - 3174. [Abstract] [Full Text] [PDF]

				J. A. McLear, D. Lebrecht, A. Messer, and W. J. Wolfgang Combinational approach of intrabody with enhanced Hsp70 expression addresses multiple pathologies in a fly model of Huntington's disease FASEB J, June 1, 2008; 22(6): 2003 - 2011. [Abstract] [Full Text] [PDF]