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Immunotherapy targe...
Immunotherapy targeting α-synuclein protofibrils reduced pathology in (Thy-1)-h[A30P] α-synuclein mice
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- Lindström, Veronica (author)
- Uppsala universitet,Geriatrik,Lannfelt
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- Fagerqvist, Therese (author)
- Uppsala universitet,Geriatrik,Lannfelt
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- Eva, Nordström (author)
- BioArctic Neuroscience AB
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- Eriksson, Fredrik (author)
- BioArctic Neuroscience AB
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- Lord, Anna (author)
- BioArctic Neuroscience AB
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- Tucker, Stina (author)
- BioArctic Neuroscience AB
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- Anderssson, Jessica (author)
- BioArctic Neuroscience AB
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- Johannesson, Malin (author)
- BioArctic Neuroscience AB
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- Schell, Heinrich (author)
- Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases, Tübingen
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- Kahle, Philipp J (author)
- Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases, Tübingen
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- Möller, Christer (author)
- BioArctic Neuroscience AB
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- Gellerfors, Pär (author)
- BioArctic Neuroscience AB
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- Bergström, Joakim (author)
- Uppsala universitet,Geriatrik,Lannfelt
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- Lannfelt, Lars (author)
- Uppsala universitet,Geriatrik,Lannfelt
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- Ingelsson, Martin (author)
- Uppsala universitet,Geriatrik,Lannfelt
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(creator_code:org_t)
- Elsevier BV, 2014
- 2014
- English.
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In: Neurobiology of Disease. - : Elsevier BV. - 0969-9961 .- 1095-953X. ; 69, s. 134-143
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Several lines of evidence suggest that accumulation of aggregated alpha-synuclein (α-synuclein) in the central nervous system (CNS) is an early pathogenic event and therefore a suitable therapeutic target in Parkinson’s disease and other Lewy body disorders. In recent years, animal studies have indicated immunotherapy with antibodies directed against α-synuclein as a promising novel treatment strategy. Since large α-synuclein oligomers, or protofibrils, have been demonstrated to possess pronounced cytotoxic properties, such species should be particularly attractive as therapeutic targets. An α-synuclein protofibril-selective monoclonal antibody, mAb47, was evaluated in the (Thy-1)-h[A30P] α-synuclein transgenic mouse model, featuring an age- and motor dysfunction-associated increase of α-synuclein protofibrils in the CNS. As measured by ELISA, mAb47-treated mice displayed significantly lower levels of both soluble and membrane-associated protofibrils in the spinal cord. In addition, a trend for increased survival as a result of reduced motor symptoms was observed with antibody treatment. Taken together, this study demonstrates reduced levels of pathogenic α-synuclein and indicates a reduction of motor dysfunction in transgenic mice upon peripheral administration of an α-synuclein protofibril-selective antibody. Thus, immunotherapy with antibodies targeting toxic α-synuclein species holds promise as a future disease-modifying treatment in Parkinson’s disease and related disorders.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Alpha-synuclein
- Parkinson´s disease
- Oligomers
- Monoclonal antibody
- Immunotherapy
- Neuroscience
- Neurovetenskap
- Geriatrics
- Geriatrik
Publication and Content Type
- ref (subject category)
- art (subject category)
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Lindström, Veron ...
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Fagerqvist, Ther ...
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Eva, Nordström
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Eriksson, Fredri ...
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Lord, Anna
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Tucker, Stina
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Anderssson, Jess ...
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Johannesson, Mal ...
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Schell, Heinrich
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Kahle, Philipp J
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Möller, Christer
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Gellerfors, Pär
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Bergström, Joaki ...
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Lannfelt, Lars
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Ingelsson, Marti ...
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MEDICAL AND HEAL ...
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Uppsala University