Alpha-synuclein oligomer-selective antibodies reduce intracellular accumulation and mitochondrial impairment in alpha-synuclein exposed astrocytes
Abstract Background Due to its neurotoxic properties, oligomeric alpha-synuclein (α-syn) has been suggested as an attractive target for passive immunization against Parkinson’s disease (PD). In mouse models of PD, antibody treatment has been shown to lower the levels of pathogenic α-syn species, inc...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-12-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-017-1018-z |
| _version_ | 1818932953996066816 |
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| author | Gabriel Gustafsson Veronica Lindström Jinar Rostami Eva Nordström Lars Lannfelt Joakim Bergström Martin Ingelsson Anna Erlandsson |
| author_facet | Gabriel Gustafsson Veronica Lindström Jinar Rostami Eva Nordström Lars Lannfelt Joakim Bergström Martin Ingelsson Anna Erlandsson |
| author_sort | Gabriel Gustafsson |
| collection | DOAJ |
| description | Abstract Background Due to its neurotoxic properties, oligomeric alpha-synuclein (α-syn) has been suggested as an attractive target for passive immunization against Parkinson’s disease (PD). In mouse models of PD, antibody treatment has been shown to lower the levels of pathogenic α-syn species, including oligomers, although the mechanisms of action remain unknown. We have previously shown that astrocytes rapidly engulf α-syn oligomers that are intracellularly stored, rather than degraded, resulting in impaired mitochondria. Methods The aim of the present study was to investigate if the accumulation of α-syn in astrocytes can be affected by α-syn oligomer-selective antibodies. Co-cultures of astrocytes, neurons, and oligodendrocytes were derived from embryonic mouse cortex and exposed to α-syn oligomers or oligomers pre-incubated with oligomer-selective antibodies. Results In the presence of antibodies, the astrocytes displayed an increased clearance of the exogenously added α-syn, and consequently, the α-syn accumulation in the culture was markedly reduced. Moreover, the addition of antibodies rescued the astrocytes from the oligomer-induced mitochondrial impairment. Conclusions Our results demonstrate that oligomer-selective antibodies can prevent α-syn accumulation and mitochondrial dysfunction in cultured astrocytes. |
| first_indexed | 2024-12-20T04:40:41Z |
| format | Article |
| id | doaj.art-6b2f7e0c7db945cfba52129a3a2cf461 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-20T04:40:41Z |
| publishDate | 2017-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-6b2f7e0c7db945cfba52129a3a2cf4612022-12-21T19:53:08ZengBMCJournal of Neuroinflammation1742-20942017-12-0114111410.1186/s12974-017-1018-zAlpha-synuclein oligomer-selective antibodies reduce intracellular accumulation and mitochondrial impairment in alpha-synuclein exposed astrocytesGabriel Gustafsson0Veronica Lindström1Jinar Rostami2Eva Nordström3Lars Lannfelt4Joakim Bergström5Martin Ingelsson6Anna Erlandsson7Molecular Geriatrics, Department of Public Health and Caring Sciences, Rudbeck Laboratory, Uppsala UniversityMolecular Geriatrics, Department of Public Health and Caring Sciences, Rudbeck Laboratory, Uppsala UniversityMolecular Geriatrics, Department of Public Health and Caring Sciences, Rudbeck Laboratory, Uppsala UniversityBioArctic ABMolecular Geriatrics, Department of Public Health and Caring Sciences, Rudbeck Laboratory, Uppsala UniversityMolecular Geriatrics, Department of Public Health and Caring Sciences, Rudbeck Laboratory, Uppsala UniversityMolecular Geriatrics, Department of Public Health and Caring Sciences, Rudbeck Laboratory, Uppsala UniversityMolecular Geriatrics, Department of Public Health and Caring Sciences, Rudbeck Laboratory, Uppsala UniversityAbstract Background Due to its neurotoxic properties, oligomeric alpha-synuclein (α-syn) has been suggested as an attractive target for passive immunization against Parkinson’s disease (PD). In mouse models of PD, antibody treatment has been shown to lower the levels of pathogenic α-syn species, including oligomers, although the mechanisms of action remain unknown. We have previously shown that astrocytes rapidly engulf α-syn oligomers that are intracellularly stored, rather than degraded, resulting in impaired mitochondria. Methods The aim of the present study was to investigate if the accumulation of α-syn in astrocytes can be affected by α-syn oligomer-selective antibodies. Co-cultures of astrocytes, neurons, and oligodendrocytes were derived from embryonic mouse cortex and exposed to α-syn oligomers or oligomers pre-incubated with oligomer-selective antibodies. Results In the presence of antibodies, the astrocytes displayed an increased clearance of the exogenously added α-syn, and consequently, the α-syn accumulation in the culture was markedly reduced. Moreover, the addition of antibodies rescued the astrocytes from the oligomer-induced mitochondrial impairment. Conclusions Our results demonstrate that oligomer-selective antibodies can prevent α-syn accumulation and mitochondrial dysfunction in cultured astrocytes.http://link.springer.com/article/10.1186/s12974-017-1018-zα-synuclein oligomersAstrocytesAntibodiesMitochondriaLysosomal degradationParkinson’s disease |
| spellingShingle | Gabriel Gustafsson Veronica Lindström Jinar Rostami Eva Nordström Lars Lannfelt Joakim Bergström Martin Ingelsson Anna Erlandsson Alpha-synuclein oligomer-selective antibodies reduce intracellular accumulation and mitochondrial impairment in alpha-synuclein exposed astrocytes Journal of Neuroinflammation α-synuclein oligomers Astrocytes Antibodies Mitochondria Lysosomal degradation Parkinson’s disease |
| title | Alpha-synuclein oligomer-selective antibodies reduce intracellular accumulation and mitochondrial impairment in alpha-synuclein exposed astrocytes |
| title_full | Alpha-synuclein oligomer-selective antibodies reduce intracellular accumulation and mitochondrial impairment in alpha-synuclein exposed astrocytes |
| title_fullStr | Alpha-synuclein oligomer-selective antibodies reduce intracellular accumulation and mitochondrial impairment in alpha-synuclein exposed astrocytes |
| title_full_unstemmed | Alpha-synuclein oligomer-selective antibodies reduce intracellular accumulation and mitochondrial impairment in alpha-synuclein exposed astrocytes |
| title_short | Alpha-synuclein oligomer-selective antibodies reduce intracellular accumulation and mitochondrial impairment in alpha-synuclein exposed astrocytes |
| title_sort | alpha synuclein oligomer selective antibodies reduce intracellular accumulation and mitochondrial impairment in alpha synuclein exposed astrocytes |
| topic | α-synuclein oligomers Astrocytes Antibodies Mitochondria Lysosomal degradation Parkinson’s disease |
| url | http://link.springer.com/article/10.1186/s12974-017-1018-z |
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