Abstract
Aggregation of alpha-synuclein (alpha-SYN) plays a key role in Parkinson's disease. We have previously shown that aggregation of alpha-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 alpha-SYN. FKBP12 has a much smaller effect on the fibril formation of these two clinical mutants alpha-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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Substitution
-
Brain / metabolism*
-
Brain / pathology
-
Brain / physiopathology
-
Catalytic Domain / genetics
-
Cell Line, Tumor
-
Humans
-
Immunosuppressive Agents / pharmacology
-
Mutation / genetics
-
Nerve Degeneration / genetics
-
Nerve Degeneration / metabolism*
-
Nerve Degeneration / physiopathology
-
Neurofibrillary Tangles / drug effects
-
Neurofibrillary Tangles / genetics
-
Neurofibrillary Tangles / metabolism*
-
Neurons / drug effects
-
Neurons / metabolism*
-
Neurons / pathology
-
Nonlinear Dynamics
-
Parkinson Disease / genetics
-
Parkinson Disease / metabolism
-
Parkinson Disease / physiopathology
-
Tacrolimus / pharmacology
-
Tacrolimus Binding Protein 1A / genetics
-
Tacrolimus Binding Protein 1A / metabolism*
-
Tacrolimus Binding Protein 1A / pharmacology
-
Time Factors
-
alpha-Synuclein / drug effects
-
alpha-Synuclein / genetics
-
alpha-Synuclein / metabolism*
Substances
-
Immunosuppressive Agents
-
alpha-Synuclein
-
Tacrolimus Binding Protein 1A
-
Tacrolimus