کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2188399 1096166 2007 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Isolation of a Human Single Chain Antibody Fragment Against Oligomeric α-Synuclein that Inhibits Aggregation and Prevents α-Synuclein-induced Toxicity
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Isolation of a Human Single Chain Antibody Fragment Against Oligomeric α-Synuclein that Inhibits Aggregation and Prevents α-Synuclein-induced Toxicity
چکیده انگلیسی

Protein misfolding and aggregation are pathological aspects of numerous neurodegenerative diseases. Aggregates of α-synuclein are major components of the Lewy bodies and Lewy neurites associated with Parkinson's Disease (PD). A natively unfolded protein, α-synuclein can adopt different aggregated morphologies, including oligomers, protofibrils and fibrils. The small oligomeric aggregates have been shown to be particularly toxic. Antibodies that neutralize the neurotoxic aggregates without interfering with beneficial functions of monomeric α-synuclein can be useful therapeutics. We were able to isolate single chain antibody fragments (scFvs) from a phage displayed antibody library against the target antigen morphology using a novel biopanning technique that utilizes atomic force microscopy (AFM) to image and immobilize specific morphologies of α-synuclein. The scFv described here binds only to an oligomeric form of α-synuclein and inhibits both aggregation and toxicity of α-synuclein in vitro. This scFv can have potential therapeutic value in controlling misfolding and aggregation of α-synuclein in vivo when expressed intracellularly in dopaminergic neurons as an intrabody.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Biology - Volume 368, Issue 4, 11 May 2007, Pages 1132–1144
نویسندگان
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