Rabenstein, Monika, Agbo, Daniela Besong, Wolf, Elias, Dams, Judith, Nicolai, Marina, Roeder, Andreas, Bacher, Michael, Dodel, Richard C. and Noelker, Carmen (2019). Effect of naturally occurring alpha-synuclein-antibodies on toxic alpha-synuclein-fragments. Neurosci. Lett., 704. S. 181 - 189. CLARE: ELSEVIER IRELAND LTD. ISSN 1872-7972

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Abstract

Alpha-synuclein (alpha-Syn) is a soluble protein primarily expressed in presynaptic terminals in the central nervous system (CNS). Aggregates of fibrillated alpha-Syn are the major component of Lewy bodies (LB), a pathologic hallmark of idiopathic Parkinson's disease (PD). Recently, naturally occurring autoantibodies against human alpha-Syn (nAbs alpha-Syn) were detected in the peripheral blood of PD patients and controls. Here, we investigated the inhibitory effects of nAbs alpha-Syn on distinct alpha-Syn fragments, as well as inflammatory responses and cytotoxicity evoked by nAbs alpha-Syn in primary microglia. All alpha-Syn fragments induced the release of the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) from microglia in primary culture. Cotreatment with nAbs alpha-Syn alleviated the release of pro-inflammatory cytokines induced by alpha-Syn fragments alpha-Syn 1-95, alpha-Syn 61-140, alpha-Syn 96-140 and alpha-Syn 112. Treatment with the alpha-Syn fragments alpha-Syn 1-95, alpha-Syn 61-140 and alpha-Syn 112 impaired the viability of primary microglia. This effect could not be counteracted by cotreatment with nAbs alpha-Syn. Data suggest an important role of nAbs alpha-Syn in the alpha-Syn-induced inflammation cascade, and indicate the potential importance of nAbs in the pathogenesis of PD. This could provide an experimental therapeutic target for patients with PD.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Rabenstein, MonikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Agbo, Daniela BesongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, EliasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dams, JudithUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nicolai, MarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roeder, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bacher, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dodel, Richard C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noelker, CarmenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-137506
DOI: 10.1016/j.neulet.2019.04.004
Journal or Publication Title: Neurosci. Lett.
Volume: 704
Page Range: S. 181 - 189
Date: 2019
Publisher: ELSEVIER IRELAND LTD
Place of Publication: CLARE
ISSN: 1872-7972
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; BETA-SHEET; ACTIVATES MICROGLIA; SUBSTANTIA-NIGRA; AGGREGATION; IMMUNIZATION; BRAIN; AUTOANTIBODIES; INFLAMMATIONMultiple languages
NeurosciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13750

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