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Immunization Effects of a Novel α-Synuclein-Based Peptide Epitope Vaccine in Parkinson’s Disease-Associated Pathologyopen access

Authors
Park, Jun SungAhmad, RiazChoe, KyonghwanKang, Min HwaPark, Tae JuKim, Myeong Ok
Issue Date
Dec-2023
Publisher
Multidisciplinary Digital Publishing Institute (MDPI)
Keywords
epitope; immunization; neuroinflammation; Parkinson’s disease (PD); α-synuclein
Citation
Vaccines, v.11, no.12
Indexed
SCIE
SCOPUS
Journal Title
Vaccines
Volume
11
Number
12
URI
https://scholarworks.gnu.ac.kr/handle/sw.gnu/69109
DOI
10.3390/vaccines11121820
ISSN
2076-393X
2076-393X
Abstract
Parkinson’s disease (PD) is a chronic neurodegenerative disease that affects the central nervous system, specifically the motor system. It is mainly caused by the loss of dopamine due to the accumulation of α-synuclein (α-syn) protein in the striatum and substantia nigra pars compacta (SNpc). Previous studies have reported that immunization may be a potential preventive strategy for neurodegenerative diseases such as Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). Therefore, the aim of the study was to design an α-syn specific epitope vaccine and investigate its effect in PD-related pathophysiology using an α-syn-induced mouse model. We used an in silico model to identify and design a non-toxic α-syn-based peptide epitope vaccine and, to overcome poor immunogenicity, the vaccine was coupled with immunogenic carrier proteins, i.e., ovalbumin (OVA) and keyhole limpet haemocyanin (KLH). Our results showed that vaccinated PD mouse models, especially with vaccines with carrier proteins, improved in motor functions compared with the non-vaccinated PD model. Additionally, the vaccinated groups showed increased immunoglobulin G (IgG) levels in the spleen and plasma as well as decreased interleukin-10 (IL-10) levels in the plasma. Furthermore, vaccinated groups, especially OVA and KLH groups, showed decrease in α-syn levels and increased dopamine-related markers, i.e., tyrosine hydroxylase (TH), vesicle monoamine transporter 2 (VMAT2), and dopamine transporter (DAT), and autophagy activities in the striatum and SNpc. Lastly, our data showed decreased neuroinflammation by reducing the activation of microglia and astrocytes and pro-inflammatory cytokines in the immunized groups, especially with OVA and KLH carrier proteins. Overall, these results suggest that vaccination, especially with immunogenic carrier proteins, is effective in reducing the accumulation of α-syn aggregates in the brain and ameliorate PD-related pathophysiology. Hence, further development of this approach might have a potential role in preventing the development of PD. © 2023 by the authors.
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