Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Rabenstein, Monika UNSPECIFIED UNSPECIFIED UNSPECIFIED Agbo, Daniela Besong UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Elias UNSPECIFIED UNSPECIFIED UNSPECIFIED Dams, Judith UNSPECIFIED UNSPECIFIED UNSPECIFIED Nicolai, Marina UNSPECIFIED UNSPECIFIED UNSPECIFIED Roeder, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Bacher, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Dodel, Richard C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Noelker, Carmen UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; BETA-SHEET; ACTIVATES MICROGLIA; SUBSTANTIA-NIGRA; AGGREGATION; IMMUNIZATION; BRAIN; AUTOANTIBODIES; INFLAMMATION Multiple languages Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13750