Autoren:	Wilding, Corina Bell, Katharina Beck, Sabine Funke, Sebastian Pfeiffer, Norbert Grus, Franz-Hermann
Titel:	gamma-Synuclein antibodies have neuroprotective potential on neuroretinal cells via proteins of the mitochondrial apoptosis pathway
Online-Publikationsdatum:	14-Jul-2022
Erscheinungsdatum:	2014
Sprache des Dokuments:	Englisch
Zusammenfassung/Abstract:	The family of synuclein proteins (alpha, beta and gamma) are related to neurodegenerative disease e.g. Parkinson disease and Morbus Alzheimer. Additionally, a connection between gamma-synuclein and glaucoma, a neurodegenerative disease characterized by a progressive loss of retinal ganglion cells, which finally leads to blindness, exists. The reason for the development of glaucoma is still unknown. Recent studies evaluating the participation of immunological components, demonstrate complex changed antibody reactivities in glaucoma patients in comparison to healthy people, showing not only up-regulations (e.g. alpha-fodrin antibody) but also down-regulations (e.g. gamma-synuclein antibody) of antibodies in glaucoma patients. Up-regulated antibodies could be auto-aggressive, but the role of down-regulated antibodies is still unclear. Previous studies show a significant influence of the serum and the antibodies of glaucoma patients on protein expression profiles of neuroretinal cells. The aim of this study was to investigate the effect of gamma-synuclein antibody on the viability and reactive oxygen species levels of a neuroretinal cell line (RGC-5) as well as their interaction with cellular proteins. We found a protective effect of gamma-synuclein antibody resulting in an increased viability (up to 15%) and decreased reactive oxygen species levels (up to -12%) of glutamate and oxidative stressed RGC-5. These can be traced back to anti-apoptotic altered protein expressions in the mitochondrial apoptosis pathway indicated by mass spectrometry and validated by microarray analysis such as active caspase 3, bcl-2 associated-x-protein, S100A4, voltage-dependent anion channel, extracellular-signal-regulated-kinase (down-regulated) and baculoviral IAP repeat-containing protein 6, phosphorylated extracellular-signal-regulated-kinase (up-regulated). These changed protein expression are triggered by the gamma-synuclein antibody internalization of RGC-5 we could see in immunohistochemical stainings. These findings let us assume a novel physiological function of gamma-synuclein antibodies and give insights in the role of autoantibodies in glaucoma. We hypothesize that the down-regulation of autoantibodies found in glaucoma patients lead to a loss of protective autoimmunity.
DDC-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7422
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	PLoS one 9 3
Seitenzahl oder Artikelnummer:	e90737
Verlag:	PLoS
Verlagsort:	Lawrence, Kan.
Erscheinungsdatum:	2014
ISSN:	1932-6203
URL der Originalveröffentlichung:	http://dx.doi.org/10.1371/journal.pone.0090737
DOI der Originalveröffentlichung:	10.1371/journal.pone.0090737
Enthalten in den Sammlungen:	DFG-OA-Publizieren (2012 - 2017)