Autoantibodies against α-synuclein inhibit its aggregation and cytotoxicity.
Autoantibodies against α-synuclein inhibit its aggregation and cytotoxicity.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
DE · Author affiliation · country only
Department of Neurology, Philipps-University Marburg, Rudolf-Bultmann Strasse 8, 35033, Marburg, Germany.Location evidence
Munich, DE · Author affiliation
Institute of Pathology, Neuperlach, Munich, Germany.Location evidence
Frankfurt am Main, DE · Author affiliation
Department of Neurology, Philipps-University Marburg, Rudolf-Bultmann Strasse 8, 35033, Marburg, Germany; Dr. Senckenbergische Anatomy, Goethe University Frankfurt, Theodor Stern Kay 7, 60590, Frankfurt am Main, Germany.Location evidence
Essen, DE · Author affiliation
Chair of Geriatric Medicine, University Duisburg-Essen, Essen, Germany.Location evidence
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Original abstract
Aggregates of α-synuclein (α-Syn) are the major component of the Lewy bodies associated with Parkinson's disease. Recently, naturally occurring autoantibodies against α-synuclein (α-Syn-nAbs) were detected. Herein we have isolated and further characterized such α-Syn-nAbs. Using an affinity column coated with α-Syn, we have isolated α-Syn-nAbs from a commercially available intravenous Immunoglobulin (IVIg) preparation. A methodological approach based on ELISA, Western blotting and immunoprecipitation as well as surface plasmon resonance, was used to determine binding capacity to α-Syn. The epitope was determined via peptide array membrane and the functionality was tested in vitro using a toxicity and a fibrillation assay. The autoantibodies display strong binding capacity to α-Syn as demonstrated by ELISA, immunoprecipitation and Western blotting analysis. The binding affinities of the purified autoantibodies were analyzed in detail by surface plasmon resonance (Biacore). The epitope on α-Syn that is recognized by the α-Syn nAbs was fully determined. A sequence within the non-amyloid component (NAC)-Region of α-Syn is crucial for the binding of α-Syn-nAbs to α-Syn. Furthermore, the α-Syn-nAbs had an inhibitory effect on α-Syn fibril formation and were also able to specifically reverse the toxicity of α-Syn oligomers species in human neuroblastoma (SH-SY5Y) cells. Our results emphasize the possible importance of naturally occurring autoantibodies for the pathogenesis of Parkinson's disease. Since autoantibodies against α-Syn are detectable in human serum and cerebrospinal fluid and interfere with pathological events associated with α-Syn, they may provide a candidate for the treatment of Parkinson's disease.