Antibodies against alpha-synuclein reduce oligomerization in living cells.

Recent research implicates soluble aggregated forms of α-synuclein as neurotoxic species with a central role in the pathogenesis of Parkinson's disease and related disorders. The pathway by which α-synuclein aggregates is believed to follow a step-wise pattern, in which dimers and smaller oligo...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Thomas Näsström, Susana Gonçalves, Charlotte Sahlin, Eva Nordström, Valentina Screpanti Sundquist, Lars Lannfelt, Joakim Bergström, Tiago F Outeiro, Martin Ingelsson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/36540fddbde747e09f645e1c2d74f401
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:36540fddbde747e09f645e1c2d74f401
record_format	dspace
spelling	oai:doaj.org-article:36540fddbde747e09f645e1c2d74f4012021-11-18T07:35:19ZAntibodies against alpha-synuclein reduce oligomerization in living cells.1932-620310.1371/journal.pone.0027230https://doaj.org/article/36540fddbde747e09f645e1c2d74f4012011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22073131/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Recent research implicates soluble aggregated forms of α-synuclein as neurotoxic species with a central role in the pathogenesis of Parkinson's disease and related disorders. The pathway by which α-synuclein aggregates is believed to follow a step-wise pattern, in which dimers and smaller oligomers are initially formed. Here, we used H4 neuroglioma cells expressing α-synuclein fused to hemi:GFP constructs to study the effects of α-synuclein monoclonal antibodies on the early stages of aggregation, as quantified by Bimolecular Fluorescence Complementation assay. Widefield and confocal microscopy revealed that cells treated for 48 h with monoclonal antibodies internalized antibodies to various degrees. C-terminal and oligomer-selective α-synuclein antibodies reduced the extent of α-synuclein dimerization/oligomerization, as indicated by decreased GFP fluorescence signal. Furthermore, ELISA measurements on lysates and conditioned media from antibody treated cells displayed lower α-synuclein levels compared to untreated cells, suggesting increased protein turnover. Taken together, our results propose that extracellular administration of monoclonal antibodies can modify or inhibit early steps in the aggregation process of α-synuclein, thus providing further support for passive immunization against diseases with α-synuclein pathology.Thomas NäsströmSusana GonçalvesCharlotte SahlinEva NordströmValentina Screpanti SundquistLars LannfeltJoakim BergströmTiago F OuteiroMartin IngelssonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 10, p e27230 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Thomas Näsström Susana Gonçalves Charlotte Sahlin Eva Nordström Valentina Screpanti Sundquist Lars Lannfelt Joakim Bergström Tiago F Outeiro Martin Ingelsson Antibodies against alpha-synuclein reduce oligomerization in living cells.
description	Recent research implicates soluble aggregated forms of α-synuclein as neurotoxic species with a central role in the pathogenesis of Parkinson's disease and related disorders. The pathway by which α-synuclein aggregates is believed to follow a step-wise pattern, in which dimers and smaller oligomers are initially formed. Here, we used H4 neuroglioma cells expressing α-synuclein fused to hemi:GFP constructs to study the effects of α-synuclein monoclonal antibodies on the early stages of aggregation, as quantified by Bimolecular Fluorescence Complementation assay. Widefield and confocal microscopy revealed that cells treated for 48 h with monoclonal antibodies internalized antibodies to various degrees. C-terminal and oligomer-selective α-synuclein antibodies reduced the extent of α-synuclein dimerization/oligomerization, as indicated by decreased GFP fluorescence signal. Furthermore, ELISA measurements on lysates and conditioned media from antibody treated cells displayed lower α-synuclein levels compared to untreated cells, suggesting increased protein turnover. Taken together, our results propose that extracellular administration of monoclonal antibodies can modify or inhibit early steps in the aggregation process of α-synuclein, thus providing further support for passive immunization against diseases with α-synuclein pathology.
format	article
author	Thomas Näsström Susana Gonçalves Charlotte Sahlin Eva Nordström Valentina Screpanti Sundquist Lars Lannfelt Joakim Bergström Tiago F Outeiro Martin Ingelsson
author_facet	Thomas Näsström Susana Gonçalves Charlotte Sahlin Eva Nordström Valentina Screpanti Sundquist Lars Lannfelt Joakim Bergström Tiago F Outeiro Martin Ingelsson
author_sort	Thomas Näsström
title	Antibodies against alpha-synuclein reduce oligomerization in living cells.
title_short	Antibodies against alpha-synuclein reduce oligomerization in living cells.
title_full	Antibodies against alpha-synuclein reduce oligomerization in living cells.
title_fullStr	Antibodies against alpha-synuclein reduce oligomerization in living cells.
title_full_unstemmed	Antibodies against alpha-synuclein reduce oligomerization in living cells.
title_sort	antibodies against alpha-synuclein reduce oligomerization in living cells.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/36540fddbde747e09f645e1c2d74f401
work_keys_str_mv	AT thomasnasstrom antibodiesagainstalphasynucleinreduceoligomerizationinlivingcells AT susanagoncalves antibodiesagainstalphasynucleinreduceoligomerizationinlivingcells AT charlottesahlin antibodiesagainstalphasynucleinreduceoligomerizationinlivingcells AT evanordstrom antibodiesagainstalphasynucleinreduceoligomerizationinlivingcells AT valentinascrepantisundquist antibodiesagainstalphasynucleinreduceoligomerizationinlivingcells AT larslannfelt antibodiesagainstalphasynucleinreduceoligomerizationinlivingcells AT joakimbergstrom antibodiesagainstalphasynucleinreduceoligomerizationinlivingcells AT tiagofouteiro antibodiesagainstalphasynucleinreduceoligomerizationinlivingcells AT martiningelsson antibodiesagainstalphasynucleinreduceoligomerizationinlivingcells
_version_	1718423214389985280

Antibodies against alpha-synuclein reduce oligomerization in living cells.

Ejemplares similares