Abstract
BackgroundAuto-antibodies with specificity to self-antigens have been implicated in a wide variety of neurological diseases, including Parkinson's (PD) and Alzheimer's diseases, being sensitive indicators of neurodegeneration and focus for disease prevention. Of particular interest are the studies focused on the auto-immune responses to amyloidogenic proteins associated with diseases and their applications in therapeutic treatments such as vaccination with amyloid antigens and antibodies in PD, Alzheimer's disease and potentially other neurodegeneration ailments.Methodology/Principal FindingsGenerated auto-antibodies towards the major amyloidogenic protein involved in PD Lewy bodies – α-synuclein and its amyloid oligomers and fibrils were measured in the blood sera of early and late PD patients and controls by using ELISA, Western blot and Biacore surface plasmon resonance. We found significantly higher antibody levels towards monomeric α-synuclein in the blood sera of PD patients compared to controls, though the responses decreased with PD progression (P<0.0001). This indicates potential protective role of autoimmunity in maintaining the body homeostasis and clearing protein species whose disbalance may lead to amyloid assembly. There were no noticeable immune responses towards amyloid oligomers, but substantially increased levels of IgGs towards α-synuclein amyloid fibrils both in PD patients and controls, which subsided with the disease progression (P<0.0001). Pooled IgGs from PD patients and controls interacted also with the amyloid fibrils of Aβ (1–40) and hen lysozyme, however the latter were recognized with lower affinity. This suggests that IgGs bind to the generic amyloid conformational epitope, displaying higher specificity towards human amyloid species associated with neurodegeneration.Conclusions/SignificanceOur findings may suggest the protective role of autoimmunity in PD and therefore immune reactions towards PD major amyloid protein – α-synuclein can be of value in the development of treatment and diagnostic strategies, especially during the early disease stages.
Highlights
Protein aggregation leading to amyloid deposition in the brain is implicated in the pathology of a number of neurodegenerative diseases such as Parkinson’s (PD), Alzheimer’s (AD), prion diseases and others [1,2,3,4]
There were no significant correlations between the immune responses in PD patients and controls with their age or gender as assessed by both Enzyme linked immunosorbent assay (ELISA) and Western blot analyses
Auto-antibodies with specificity to self-antigens have been implicated in a wide variety of neurological diseases [7,8,39] including PD [9,40], as they reflect the pathological changes occurring in the brain during neurodegeneration
Summary
Protein aggregation leading to amyloid deposition in the brain is implicated in the pathology of a number of neurodegenerative diseases such as Parkinson’s (PD), Alzheimer’s (AD), prion diseases and others [1,2,3,4]. Purified IgGs from the pooled blood sera of PD patients and controls were compared with regards to their reactivity towards fibrillar antigens of different protein origin, i.e. formed from asynuclein, Ab (1–40) peptide and hen egg white lysozyme (Figure 6A), by using dot blot analysis. Both Ab (1–40) peptide and hen egg white lysozyme developed mature amyloid fibrils as described in Material and Methods and examined by AFM imaging (Figure 6B and 6C). This indicates that in blood sera of both PD patients and controls there are polyclonal IgGs reactive with conformational epitope of amyloid fibrils, targeting, primarily the fibrils associated with human neurodegenerative ailments (a-synuclein and Ab peptide)
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