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Details

Autor(en) / Beteiligte
Titel
Characterization of novel conformation-selective α-synuclein antibodies as potential immunotherapeutic agents for Parkinson's disease
Ist Teil von
  • Neurobiology of disease, 2020-03, Vol.136, p.104712-104712, Article 104712
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2020
Quelle
Access via ScienceDirect (Elsevier)
Beschreibungen/Notizen
  • Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are progressive neurodegenerative diseases for which there is no disease-modifying treatment. PD and DLB are characterized by aggregation of the synaptic protein α-synuclein, and there is compelling evidence to suggest that progression of these diseases is associated with the trans-cellular spread of pathogenic α-synuclein through the brains of afflicted individuals. Therapies targeting extracellular, pathogenic α-synuclein may therefore hold promise for slowing or halting disease progression. In this regard, it has been suggested that highly-selective antibodies can be administered as therapeutic agents targeting pathogenic proteins. In the current study, we screened a series of antibodies using multiple selection criterion to identify those that selectively bind pathogenic α-synuclein and show potent inhibition of pathology seeding in a neuronal model of α-synucleinopathy. A lead antibody was tested in a mouse model of PD, and it was able to reduce the spread of α-synuclein pathology in the brain and attenuate dopamine reductions in the striatum. This study highlights the therapeutic potential of α-synuclein immunotherapy for the treatment of PD and DLB, and provides a framework for screening of α-synuclein antibodies to identify those with preferred properties. •Conformation selective antibodies have less potential for off-target effects.•Inoculation of mice with misfolded α-synuclein generated a new class of antibodies.•Multi-assay screening identified highly selective and potent antibodies.•Lead antibody reduces α-synuclein pathology and improves dopamine in vivo.

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