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Acta Neuropathol.:新开发的抗体有望早期诊断帕金森病

来源:生物谷 2012-07-22 13:36

神经退行性疾病帕金森病当前是无法治愈的,是由于α-突触核蛋白(alpha-synuclein,也译作α-共核蛋白)发生病理性变化而产生的。在此之前,尚没有任何一种抗体能证实与这种疾病相关联的α-共核蛋白变化。如今,来自奥地利维也纳医科大学临床神经科学研究所研究员领导的一个国际专家小组发现一种新的抗体确实拥有这种能力。

在帕金森病中,致病性的α-共核蛋白与健康的α-共核蛋白白拥有相同的蛋白一级结构,但是前者会经历异常折叠。在此之前,没有人能够将两者区分开来。然而,利用研究人员开发出的这种新的单克隆抗体,能够检测到α-共核蛋白中的一个关键性部分,也正是这个关键性部分导致这种蛋白发生结构变化。这项研究的结果发表在2012年7月那期Acta Neuropathologica期刊上。

Kovacs说,“就目前而言,我们仍然不好说,我们是否能够从血液测试中诊断帕金森病,但是这些发现当然代表着一个大的进步。”从理论上讲,在这种新的抗体开发出来,人们应当能够在5到8年内利用它来诊断疾病。(生物谷:Bioon.com)

本文编译自Parkinson's: Newly discovered antibody could facilitate early diagnosis

An antibody with high reactivity for disease-associated α-synuclein reveals extensive brain pathology

Gabor G. Kovacs, Uta Wagner, Benoit Dumont, Maria Pikkarainen, Awad A. Osman, Nathalie Streichenberger, Irene Leisser, Jérémy Verchère, Thierry Baron, Irina Alafuzoff, Herbert Budka, Armand Perret-Liaudet, Ingolf Lachmann

α-Synuclein is the major protein associated with Lewy body dementia, Parkinson’s disease and multiple system atrophy. Since α-synuclein is present in the brain in physiological conditions as a presynaptic protein, it is crucial to characterize disease-associated modifications to develop an in vivo biomarker. With the aim to develop antibodies showing high specificity and sensitivity for disease-associated α-synuclein, synthetic peptides containing different amino acid sequences were used for immunization of mice. After generation of α-synuclein aggregates, ELISA and immunoblotting were used to test the specificity of antibodies. Tissue microarray sections originating from different human α-synucleinopathies were used to compare immunostaining with other, commercially available antibodies. Immunization of mice with the peptide TKEGVVHGVATVAE (amino acid 44–57 of α-synuclein) resulted in the generation of a monoclonal antibody (5G4), which was able to bind aggregated α-synuclein preparation in sandwich ELISA or coated on magnetic beads. 5G4 proved to be superior to other antibodies in comparative immunohistochemical studies by revealing more widespread and distinct α-synuclein pathology. Immunoblotting of human brain tissue revealed an additional band seen in dementia with Lewy bodies, whereas the band representing monomeric α-synuclein was very weak or lacking. In summary, the 5G4 antibody is most promising for re-evaluation of archival material and may offer new perspective for the development of in vivo diagnostic assays for detecting disease-associated α-synuclein in body fluids.

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