Title: The aggregation of alpha-synuclein is stimulated by FK506 binding proteins as shown by fluorescence correlation spectroscopy
Authors: GĂ©rard, Melanie
Debyser, Zeger
Desender, Linda
Kahle, Philipp J
Baert, Johan
Baekelandt, Veerle ×
Engelborghs, Yves #
Issue Date: Jan-2006
Publisher: The Federation of American Societies for Experimental Biology
Series Title: FASEB Journal vol:20 issue:3 pages:524-526
Abstract: Aggregation of alpha-synuclein (alpha-SYN) plays a key role in Parkinson's disease (PD). We have used fluorescence correlation spectroscopy (FCS) to study alpha-SYN aggregation in vitro and discovered that this process is clearly accelerated by addition of FK506 binding proteins (FKBPs). This effect was observed both with E. coli SlyD FKBP and with human FKBP12 and was counteracted by FK506, a specific inhibitor of FKBP. The alpha-SYN aggregates formed in the presence of FKBP12 showed fibrillar morphology. The rotamase activity of FKBP apparently accelerates the folding and subsequent aggregation of alpha-SYN. Since FK506 and other non-immunosuppressive FKBP inhibitors are known to display neuroregenerative and neuroprotective properties in disease models, the observed inhibition of rotamase activity and alpha-SYN aggregation, may explain their mode of action. Our results open perspectives for the treatment of PD with immunophilin ligands that inhibit a specific member of the FKBP family.
ISSN: 0892-6638
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Virology and Gene Therapy
Interdisciplinary Research Facility Life Sciences, Campus Kulak Kortrijk
Research Group for Neurobiology and Gene Therapy
Biochemistry, Molecular and Structural Biology Section
Biochemistry, Kulak (-)
× corresponding author
# (joint) last author

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