Peptide immunization against the C-terminal of alpha-synuclein reduces locomotor activity in mice overexpressing alpha-synuclein.
Abnormal accumulation of alpha-synuclein (αSyn) in the remaining nigra dopaminergic neurons is a common neuropathological feature found in patients with Parkinson's disease (PD). Antibody-based immunotherapy has been considered a potential approach for PD treatment. This study aims to investiga...
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Format: | Article |
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Public Library of Science (PLoS)
2023-01-01
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Series: | PLoS ONE |
Online Access: | https://doi.org/10.1371/journal.pone.0291927 |
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author | Yu-Sung Chiu Kuo-Jen Wu Seong-Jin Yu Kun-Lieh Wu Yu-Syuan Wang Jing Lin Chia-Ying Chu Shuchun Chen Hsi Chen Shu-Ching Hsu Yun Wang Yun-Hsiang Chen |
author_facet | Yu-Sung Chiu Kuo-Jen Wu Seong-Jin Yu Kun-Lieh Wu Yu-Syuan Wang Jing Lin Chia-Ying Chu Shuchun Chen Hsi Chen Shu-Ching Hsu Yun Wang Yun-Hsiang Chen |
author_sort | Yu-Sung Chiu |
collection | DOAJ |
description | Abnormal accumulation of alpha-synuclein (αSyn) in the remaining nigra dopaminergic neurons is a common neuropathological feature found in patients with Parkinson's disease (PD). Antibody-based immunotherapy has been considered a potential approach for PD treatment. This study aims to investigate the effectiveness of active immunization against αSyn in a mouse model of PD. Adult mice were immunized with or without a synthetic peptide containing the C-terminal residues of human αSyn and activation epitopes, followed by an intranigral injection of adeno-associated virus vectors for overexpressing human αSyn. Upon the peptide injection, αSyn-specific antibodies were raised, accompanied by degeneration of dopaminergic neurons and motor deficits. Furthermore, the induction of neuroinflammation was postulated by the elevation of astroglial and microglial markers in the immunized mice. Instead of lessening αSyn toxicity, this peptide vaccine caused an increase in the pathogenic species of αSyn. Our data demonstrated the potential adverse effects of active immunization to raise antibodies against the C-terminal fragment of αSyn. This drawback highlights the need for further investigation to weigh the pros and cons of immunotherapy in PD. Applying the αSyn C-terminal peptide vaccine for PD treatment should be cautiously exercised. This study provides valuable insights into the intricate interplay among immune intervention, αSyn accumulation, and neurodegeneration. |
first_indexed | 2024-03-11T21:21:54Z |
format | Article |
id | doaj.art-5f7caeedfc2c4212b652a0008bb8fced |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-03-11T21:21:54Z |
publishDate | 2023-01-01 |
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series | PLoS ONE |
spelling | doaj.art-5f7caeedfc2c4212b652a0008bb8fced2023-09-28T05:31:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01189e029192710.1371/journal.pone.0291927Peptide immunization against the C-terminal of alpha-synuclein reduces locomotor activity in mice overexpressing alpha-synuclein.Yu-Sung ChiuKuo-Jen WuSeong-Jin YuKun-Lieh WuYu-Syuan WangJing LinChia-Ying ChuShuchun ChenHsi ChenShu-Ching HsuYun WangYun-Hsiang ChenAbnormal accumulation of alpha-synuclein (αSyn) in the remaining nigra dopaminergic neurons is a common neuropathological feature found in patients with Parkinson's disease (PD). Antibody-based immunotherapy has been considered a potential approach for PD treatment. This study aims to investigate the effectiveness of active immunization against αSyn in a mouse model of PD. Adult mice were immunized with or without a synthetic peptide containing the C-terminal residues of human αSyn and activation epitopes, followed by an intranigral injection of adeno-associated virus vectors for overexpressing human αSyn. Upon the peptide injection, αSyn-specific antibodies were raised, accompanied by degeneration of dopaminergic neurons and motor deficits. Furthermore, the induction of neuroinflammation was postulated by the elevation of astroglial and microglial markers in the immunized mice. Instead of lessening αSyn toxicity, this peptide vaccine caused an increase in the pathogenic species of αSyn. Our data demonstrated the potential adverse effects of active immunization to raise antibodies against the C-terminal fragment of αSyn. This drawback highlights the need for further investigation to weigh the pros and cons of immunotherapy in PD. Applying the αSyn C-terminal peptide vaccine for PD treatment should be cautiously exercised. This study provides valuable insights into the intricate interplay among immune intervention, αSyn accumulation, and neurodegeneration.https://doi.org/10.1371/journal.pone.0291927 |
spellingShingle | Yu-Sung Chiu Kuo-Jen Wu Seong-Jin Yu Kun-Lieh Wu Yu-Syuan Wang Jing Lin Chia-Ying Chu Shuchun Chen Hsi Chen Shu-Ching Hsu Yun Wang Yun-Hsiang Chen Peptide immunization against the C-terminal of alpha-synuclein reduces locomotor activity in mice overexpressing alpha-synuclein. PLoS ONE |
title | Peptide immunization against the C-terminal of alpha-synuclein reduces locomotor activity in mice overexpressing alpha-synuclein. |
title_full | Peptide immunization against the C-terminal of alpha-synuclein reduces locomotor activity in mice overexpressing alpha-synuclein. |
title_fullStr | Peptide immunization against the C-terminal of alpha-synuclein reduces locomotor activity in mice overexpressing alpha-synuclein. |
title_full_unstemmed | Peptide immunization against the C-terminal of alpha-synuclein reduces locomotor activity in mice overexpressing alpha-synuclein. |
title_short | Peptide immunization against the C-terminal of alpha-synuclein reduces locomotor activity in mice overexpressing alpha-synuclein. |
title_sort | peptide immunization against the c terminal of alpha synuclein reduces locomotor activity in mice overexpressing alpha synuclein |
url | https://doi.org/10.1371/journal.pone.0291927 |
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