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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 investigate th...

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Autores principales: Chiu, Yu-Sung, Wu, Kuo-Jen, Yu, Seong-Jin, Wu, Kun-Lieh, Wang, Yu-Syuan, Lin, Jing, Chu, Chia-Ying, Chen, Shuchun, Chen, Hsi, Hsu, Shu-Ching, Wang, Yun, Chen, Yun-Hsiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10513202/
https://www.ncbi.nlm.nih.gov/pubmed/37733672
http://dx.doi.org/10.1371/journal.pone.0291927
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author Chiu, Yu-Sung
Wu, Kuo-Jen
Yu, Seong-Jin
Wu, Kun-Lieh
Wang, Yu-Syuan
Lin, Jing
Chu, Chia-Ying
Chen, Shuchun
Chen, Hsi
Hsu, Shu-Ching
Wang, Yun
Chen, Yun-Hsiang
author_facet Chiu, Yu-Sung
Wu, Kuo-Jen
Yu, Seong-Jin
Wu, Kun-Lieh
Wang, Yu-Syuan
Lin, Jing
Chu, Chia-Ying
Chen, Shuchun
Chen, Hsi
Hsu, Shu-Ching
Wang, Yun
Chen, Yun-Hsiang
author_sort Chiu, Yu-Sung
collection PubMed
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.
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spelling pubmed-105132022023-09-22 Peptide immunization against the C-terminal of alpha-synuclein reduces locomotor activity in mice overexpressing alpha-synuclein Chiu, Yu-Sung Wu, Kuo-Jen Yu, Seong-Jin Wu, Kun-Lieh Wang, Yu-Syuan Lin, Jing Chu, Chia-Ying Chen, Shuchun Chen, Hsi Hsu, Shu-Ching Wang, Yun Chen, Yun-Hsiang PLoS One Research Article 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. Public Library of Science 2023-09-21 /pmc/articles/PMC10513202/ /pubmed/37733672 http://dx.doi.org/10.1371/journal.pone.0291927 Text en © 2023 Chiu et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Chiu, Yu-Sung
Wu, Kuo-Jen
Yu, Seong-Jin
Wu, Kun-Lieh
Wang, Yu-Syuan
Lin, Jing
Chu, Chia-Ying
Chen, Shuchun
Chen, Hsi
Hsu, Shu-Ching
Wang, Yun
Chen, Yun-Hsiang
Peptide immunization against the C-terminal of alpha-synuclein reduces locomotor activity in mice overexpressing alpha-synuclein
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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10513202/
https://www.ncbi.nlm.nih.gov/pubmed/37733672
http://dx.doi.org/10.1371/journal.pone.0291927
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