کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3064977 1580460 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Immunodominant epitope and properties of pyroglutamate-modified Aβ-specific antibodies produced in rabbits
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Immunodominant epitope and properties of pyroglutamate-modified Aβ-specific antibodies produced in rabbits
چکیده انگلیسی

N-truncated and N-modified forms of amyloid beta (Aβ) peptide are found in diffused and dense core plaques in Alzheimer's disease (AD) and Down's syndrome patients as well as transgenic mouse models of AD. Although the pathological significance of these shortened forms Aβ is not completely understood, previous studies have demonstrated that these peptides are significantly more resistant to degradation, aggregate more rapidly in vitro and exhibit similar or, in some cases, increased toxicity in hippocampal neuronal cultures compared to the full length peptides. In the present study we further investigated the mechanisms of toxicity of one of the most abundant N-truncated/modified Aβ peptide bearing amino-terminal pyroglutamate at position 3 (AβN3(pE)). We demonstrated that AβN3(pE) oligomers induce phosphatidyl serine externalization and membrane damage in SH-SY5Y cells. Also, we produced AβN3(pE)-specific polyclonal antibodies in rabbit and identified an immunodominant epitope recognized by anti-AβN3(pE) antibodies. Our results are important for developing new immunotherapeutic compounds specifically targeting AβN3(pE) aggregates since the most commonly used immunogens in the majority of vaccines for AD have been shown to induce antibodies that recognize the N-terminal immunodominant epitope (EFRH) of the full length Aβ, which is absent in N-amino truncated peptides.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Neuroimmunology - Volume 213, Issues 1–2, 18 August 2009, Pages 39–46
نویسندگان
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