PMID- 30157279
OWN - NLM
STAT- MEDLINE
DCOM- 20190208
LR  - 20190215
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 8
DP  - 2018
TI  - Extending the functional characteristics of naturally occurring autoantibodies 
      against beta-Amyloid, Prion Protein and alpha-Synuclein.
PG  - e0202954
LID - 10.1371/journal.pone.0202954 [doi]
LID - e0202954
AB  - BACKGROUND: 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. 
      OBJECTIVE: Identification of a putative common epitope among the relevant 
      proteins beta-Amyloid, alpha-Synuclein and Prion Protein for the respective nAbs. 
      MATERIAL AND METHODS: 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 Fcgamma mediated uptake by microglial cells. RESULTS: 
      beta-Amyloid and Prion Protein fragment showed considerable binding affinity and 
      functional efficacy for all applied nAbs. Thereby, no significant difference 
      within the different nAbs was detected. In contrast, alpha-Synuclein was bound 
      exclusively by nAbs-alpha-Synuclein, which was reproduced in all binding studies. 
      Surprisingly, functional assays with alpha-Synuclein revealed no significant effect 
      of nAbs in comparison to IVIg treatment. However, all applied nAbs as well as 
      IVIg show a minimal functionality on the microglial uptake of alpha-Synuclein. 
      CONCLUSION: nAbs-Abeta, nAbs-PrP possibly display comparable affinity to the same 
      structural epitope within Abeta and PrP106-126 A117V whereas the epitope recognized 
      by nAbs-alpha-Syn is only present in alpha-Syn. The structural similarity of Abeta and PrP 
      fragment promotes the outline for an efficient antibody for the treatment of 
      several neurodegenerative disorders and extend the functional characteristics of 
      the investigated nAbs.
FAU - Albus, Alexandra
AU  - Albus A
AUID- ORCID: 0000-0002-4897-6972
AD  - Chair of Geriatrics, University Hospital Essen, University Duisburg-Essen, Essen, 
      Germany.
AD  - Department of Neurology, Philipps-University, Marburg, Germany.
FAU - Gold, Maike
AU  - Gold M
AD  - Department of Neurology, Philipps-University, Marburg, Germany.
FAU - Bach, Jan-Philipp
AU  - Bach JP
AD  - Department of Neurology, Philipps-University, Marburg, Germany.
AD  - Department of Neurology, RWTH Aachen, Aachen, Germany.
FAU - Burg-Roderfeld, Monika
AU  - Burg-Roderfeld M
AD  - Department of Hematology and Immunology, Justus-Liebig-University, Giessen, 
      Germany.
FAU - Jordens, Marit
AU  - Jordens M
AD  - Department of Neurology, Philipps-University, Marburg, Germany.
FAU - Kirchhein, Yvonne
AU  - Kirchhein Y
AD  - Department of Neurology, Philipps-University, Marburg, Germany.
FAU - Kronimus, Yannick
AU  - Kronimus Y
AD  - Chair of Geriatrics, University Hospital Essen, University Duisburg-Essen, Essen, 
      Germany.
AD  - Department of Neurology, Philipps-University, Marburg, Germany.
FAU - Mengel, David
AU  - Mengel D
AD  - Department of Neurology, Philipps-University, Marburg, Germany.
FAU - Zerr, Inga
AU  - Zerr I
AD  - Department of Neurology, University Goettingen, Goettingen, Germany.
FAU - Dodel, Richard
AU  - Dodel R
AD  - Chair of Geriatrics, University Hospital Essen, University Duisburg-Essen, Essen, 
      Germany.
AD  - Department of Neurology, Philipps-University, Marburg, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180829
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Autoantibodies)
RN  - 0 (Epitopes)
RN  - 0 (Peptide Fragments)
RN  - 0 (Prion Proteins)
RN  - 0 (alpha-Synuclein)
RN  - 0 (amyloid beta-protein (1-42))
SB  - IM
MH  - Amyloid beta-Peptides/*immunology
MH  - Animals
MH  - Autoantibodies/chemistry/*immunology
MH  - Cell Line
MH  - Epitopes/chemistry/immunology
MH  - Humans
MH  - Mice
MH  - Peptide Fragments/*immunology
MH  - Prion Proteins/*immunology
MH  - alpha-Synuclein/*immunology
PMC - PMC6114858
COIS- The authors have the following interests. The DEMPARK study was partly funded by 
      an unrestricted grant from Novartis. There are no patents, products in 
      development or marketed products to declare. This does not alter the authors' 
      adherence to all the PLOS ONE policies on sharing data and materials, as detailed 
      online in the guide for authors.
EDAT- 2018/08/30 06:00
MHDA- 2019/02/09 06:00
PMCR- 2018/08/29
CRDT- 2018/08/30 06:00
PHST- 2018/03/09 00:00 [received]
PHST- 2018/08/13 00:00 [accepted]
PHST- 2018/08/30 06:00 [entrez]
PHST- 2018/08/30 06:00 [pubmed]
PHST- 2019/02/09 06:00 [medline]
PHST- 2018/08/29 00:00 [pmc-release]
AID - PONE-D-18-07408 [pii]
AID - 10.1371/journal.pone.0202954 [doi]
PST - epublish
SO  - PLoS One. 2018 Aug 29;13(8):e0202954. doi: 10.1371/journal.pone.0202954. 
      eCollection 2018.