neuronal cells [28] [29] [30]. (DOC) pone.0090737.s003.doc (232K) GUID:?E8EB4811-FD8E-49A0-8AAA-63D8C37D6436 Abstract The family of synuclein proteins (, and ) are related to neurodegenerative disease e.g. Parkinson disease and Morbus Alzheimer. Additionally, a connection between -synuclein and glaucoma, a neurodegenerative disease characterized by a progressive loss of retinal ganglion cells, which finally prospects to blindness, exists. The reason behind the development of glaucoma is still unfamiliar. Recent studies evaluating the participation of immunological parts, demonstrate complex changed antibody reactivities in glaucoma individuals in comparison to healthy people, showing not only up-regulations (e.g. alpha-fodrin antibody) but also down-regulations (e.g. -synuclein antibody) of antibodies in glaucoma individuals. Up-regulated antibodies could be auto-aggressive, but the part of COH000 down-regulated antibodies is still unclear. Previous studies show a significant influence of the serum and the antibodies of glaucoma individuals on protein manifestation profiles of neuroretinal cells. The aim of this study was to investigate the effect of -synuclein antibody within the MKI67 viability and reactive oxygen species levels of a neuroretinal cell collection (RGC-5) as well as their connection with cellular proteins. We found a protecting effect of -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 modified 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 manifestation are triggered from the -synuclein antibody internalization of RGC-5 we could observe in immunohistochemical stainings. These findings let us presume a novel physiological function of -synuclein antibodies and give insights in the part of autoantibodies in glaucoma. We hypothesize the down-regulation of autoantibodies found in glaucoma individuals lead to a loss of protecting autoimmunity. Intro Synucleins are a family of small, cytosolic proteins consisting of -, – and -synuclein. They may be abundant in neuronal cells [1] and associated with the pathogenesis of neurodegenerative diseases. Although physiological functions of synucleins are not entirely recognized, you will find suggestions that , and -synuclein possess chaperon like activity [2]. Studies show a mutated form of -synuclein in individuals with autosomal dominating Parkinson disease [3] and as a component of plaques in Alzheimer individuals [4], [5]. Furthermore -synuclein is definitely a component of Lewy body in Parkinsons disease [6]. All synucleins are indicated in retina and optic nerve [7]. -synuclein is definitely involved in neurodegenerative and ocular diseases [8], [9] and is highly indicated in retinal ganglion cells (rgc) [10]. In comparison to healthy people, the optic nerve head and retina of glaucoma individuals show different -synuclein localizations [9], [11]. Glaucoma is definitely COH000 a heterogeneous neurodegenerative disease defined by a progressive loss of rgc, optic nerve degeneration and progressive visual field loss, which finally can lead to blindness [12]. Although glaucoma is one of the most common causes for blindness worldwide [13] the pathogenesis is still unfamiliar. A major risk factor is an elevated intraocular pressure, but 30% of individuals don’t display this manifestation [14]. Studies suggest an immunological component in the pathology of glaucoma. An increased event of paraproteins and autoantibodies against nuclear antigens like Sj?gren’s syndrom A, was demonstrated in glaucoma individuals [15]. Furthermore, studies show not only up-regulated, but also down-regulated antibodies (abdominal muscles) in glaucoma individuals. In the serum and aqueous humor of glaucoma individuals general complex autoantibody patterns against retinal and optic nerve antigens were found [16], [17] but also more specific autoantibody changes such as an up- rules of abdominal muscles against e.g. alpha foldrin [16], [17] and Hsp 70 [18], and a down-regulation of abdominal muscles against B Crystallin and Vimentin [18] leading to the conclusion that there is a role for the autoantibodies in the pathogenesis of glaucoma. Earlier studies incubating neuroretinal cells with the serum and the abdominal muscles of glaucoma individuals found changed protein manifestation patterns in cells incubated with glaucoma serum in comparison to serum from healthy COH000 people [19]. Furthermore the cells reacted in a different way for the serum after removal of IgG abdominal muscles [19]. These results underline the hypothesis that changes in the autoantibodies could play a role in the pathogenesis of the disease. One autoantibody down-regulated in glaucoma individuals is definitely targeted against -synuclein. This study targeted to investigate, which.