Extending the functional characteristics of naturally occurring autoantibodies against β-Amyloid, Prion Protein and α-Synuclein

PloS One
Alexandra AlbusRichard Dodel

Abstract

Abnormal aggregation of proteins induces neuronal cell loss in neurodegenerative disorders such as Alzheimer's Disease, Creutzfeldt-Jakob Disease and Parkinson's Disease. Specific stimuli initialize conformational changes in physiological proteins, causing intra- or extracellular protein aggregation. We and other groups have identified naturally occurring autoantibodies (nAbs) as part of the human antibody pool that are able to prevent peptide fibrillation. These nAbs show a rescue effect following exposure of toxic aggregates on neurons, and they support microglial uptake of aggregated peptides. Identification of a putative common epitope among the relevant proteins β-Amyloid, α-Synuclein and Prion Protein for the respective nAbs. Binding affinity between the aforementioned proteins and nAbs was tested by Dot Blot, ELISA and SPR-technology. Furthermore, the functionality of the protein-nAbs-complexes was studied in Thioflavin-T assays and microglial uptake experiments to study dependent inhibition of protein aggregation and enhancement of Fcγ mediated uptake by microglial cells. β-Amyloid and Prion Protein fragment showed considerable binding affinity and functional efficacy for all applied nAbs. Thereby, no significant differ...Continue Reading

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Methods Mentioned

BETA
transgenic
ELISA
FCS
FACS
X-ray
interaction array
chip
Dot Blot
Dot
Dot Blots

Software Mentioned

ProteOn Manager
Flow Jo

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