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FK506 binding protein 12 differentially accelerates fibril formation of wild type alpha-synuclein and its clinical mutants A30P or A53T |
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| Authors: | Gerard Melanie Debyser Zeger Desender Linda Baert Johan Brandt Inger Baekelandt Veerle Engelborghs Yves |
| Affiliation: | Laboratory of Biomolecular Dynamics, K. U. Leuven, Leuven, Flanders, Belgium; Laboratory for Molecular Virology and Gene Therapy, Division of Molecular Medicine and Interdisciplinary Research Center, K. U. Leuven, Kortrijk, Flanders, Belgium; Laboratory for Histology, Interdisciplinary Research Center, K. U. Leuven, Kortrijk, Flanders, Belgium; Laboratory for Medical Biochemistry, University of Antwerp, Flanders, Belgium; Laboratory for Neurobiology and Gene Therapy, Division of Molecular Medicine, KU Leuven, Flanders, Belgium |
| Abstract: | Aggregation of alpha-synuclein (α-SYN) plays a key role in Parkinson's disease. We have previously shown that aggregation of α-SYN in vitro is accelerated by addition of FK506 binding proteins (FKBP) and that this effect can be counteracted by FK506, a specific inhibitor of these enzymes. In this paper, we investigated in detail the effect of FKBP12 on early aggregation and on fibril formation of wild-type, A53T and A30P α-SYN. FKBP12 has a much smaller effect on the fibril formation of these two clinical mutants α-SYN. Using an inactive enzyme, we were able to discriminate between catalytic and non-catalytic effects that differentially influence the two processes. A model explaining non-linear concentration dependencies is proposed. |
| Keywords: | aggregation alpha-synuclein FK506 binding protein Parkinson's disease peptidyl-prolyl cis-trans isomerase |
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