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Administration of AAV-Alpha Synuclein NAC Antibody Improves Locomotor Behavior in Rats Overexpressing Alpha Synuclein
Accumulation of α-Synuclein (αSyn) in nigral dopaminergic neurons is commonly seen in patients with Parkinson′s disease (PD). We recently reported that transduction of intracellular single-chain intrabody targeting the 53–87 amino acid residues of human αSyn by recombinant adeno associated viral vec...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233769/ https://www.ncbi.nlm.nih.gov/pubmed/34205689 http://dx.doi.org/10.3390/genes12060948 |
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author | Chen, Yun-Hsiang Wu, Kuo-Jen Hsieh, Wei Harvey, Brandon K. Hoffer, Barry J. Wang, Yun Yu, Seong-Jin |
author_facet | Chen, Yun-Hsiang Wu, Kuo-Jen Hsieh, Wei Harvey, Brandon K. Hoffer, Barry J. Wang, Yun Yu, Seong-Jin |
author_sort | Chen, Yun-Hsiang |
collection | PubMed |
description | Accumulation of α-Synuclein (αSyn) in nigral dopaminergic neurons is commonly seen in patients with Parkinson′s disease (PD). We recently reported that transduction of intracellular single-chain intrabody targeting the 53–87 amino acid residues of human αSyn by recombinant adeno associated viral vector (AAV-NAC32) downregulated αSyn protein in SH-SY5Y cells and rat brain. This study characterizes the behavioral phenotype and dopaminergic protection in animals receiving AAV-NAC32. Our results show that adult DAT-Cre rats selectively overexpress αSyn in nigra dopaminergic neurons after local administration of AAV-DIO-αSyn. These animals develop PD-like phenotype, including bradykinesia and loss of tyrosine hydroxylase (TH) immunoreactivity in substantia nigra pars compacta dorsal tier (SNcd). An injection of AAV-NAC32 to nigra produces a selective antibody against αSyn and normalizes the behavior. AAV-NAC32 significantly increases TH, while reduces αSyn immunoreactivity in SNcd. Altogether, our data suggest that an AAV-mediated gene transfer of NAC32 antibody effectively antagonizes αSyn-mediated dopaminergic degeneration in nigra, which may be a promising therapeutic candidate for synucleinopathy or PD. |
format | Online Article Text |
id | pubmed-8233769 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82337692021-06-27 Administration of AAV-Alpha Synuclein NAC Antibody Improves Locomotor Behavior in Rats Overexpressing Alpha Synuclein Chen, Yun-Hsiang Wu, Kuo-Jen Hsieh, Wei Harvey, Brandon K. Hoffer, Barry J. Wang, Yun Yu, Seong-Jin Genes (Basel) Article Accumulation of α-Synuclein (αSyn) in nigral dopaminergic neurons is commonly seen in patients with Parkinson′s disease (PD). We recently reported that transduction of intracellular single-chain intrabody targeting the 53–87 amino acid residues of human αSyn by recombinant adeno associated viral vector (AAV-NAC32) downregulated αSyn protein in SH-SY5Y cells and rat brain. This study characterizes the behavioral phenotype and dopaminergic protection in animals receiving AAV-NAC32. Our results show that adult DAT-Cre rats selectively overexpress αSyn in nigra dopaminergic neurons after local administration of AAV-DIO-αSyn. These animals develop PD-like phenotype, including bradykinesia and loss of tyrosine hydroxylase (TH) immunoreactivity in substantia nigra pars compacta dorsal tier (SNcd). An injection of AAV-NAC32 to nigra produces a selective antibody against αSyn and normalizes the behavior. AAV-NAC32 significantly increases TH, while reduces αSyn immunoreactivity in SNcd. Altogether, our data suggest that an AAV-mediated gene transfer of NAC32 antibody effectively antagonizes αSyn-mediated dopaminergic degeneration in nigra, which may be a promising therapeutic candidate for synucleinopathy or PD. MDPI 2021-06-21 /pmc/articles/PMC8233769/ /pubmed/34205689 http://dx.doi.org/10.3390/genes12060948 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chen, Yun-Hsiang Wu, Kuo-Jen Hsieh, Wei Harvey, Brandon K. Hoffer, Barry J. Wang, Yun Yu, Seong-Jin Administration of AAV-Alpha Synuclein NAC Antibody Improves Locomotor Behavior in Rats Overexpressing Alpha Synuclein |
title | Administration of AAV-Alpha Synuclein NAC Antibody Improves Locomotor Behavior in Rats Overexpressing Alpha Synuclein |
title_full | Administration of AAV-Alpha Synuclein NAC Antibody Improves Locomotor Behavior in Rats Overexpressing Alpha Synuclein |
title_fullStr | Administration of AAV-Alpha Synuclein NAC Antibody Improves Locomotor Behavior in Rats Overexpressing Alpha Synuclein |
title_full_unstemmed | Administration of AAV-Alpha Synuclein NAC Antibody Improves Locomotor Behavior in Rats Overexpressing Alpha Synuclein |
title_short | Administration of AAV-Alpha Synuclein NAC Antibody Improves Locomotor Behavior in Rats Overexpressing Alpha Synuclein |
title_sort | administration of aav-alpha synuclein nac antibody improves locomotor behavior in rats overexpressing alpha synuclein |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233769/ https://www.ncbi.nlm.nih.gov/pubmed/34205689 http://dx.doi.org/10.3390/genes12060948 |
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