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腾讯登录新型抗体或可帮助开发帕金森疾病的诊断和治疗手段
| 导读 | 近日，来自维也纳医科大学的研究人员利用一种新型抗体首次成功揭示了帕金森疾病在人类大脑细胞间扩散的分子机制，截止到现在，研究人员仅在实验动物体内观察到了帕金森疾病的扩散，而本文研究者首次在人类大脑中揭示了该疾病的扩散机制，相关研究刊登于国际杂志Neurobiology of Disease上。 |
近日，来自维也纳医科大学的研究人员利用一种新型抗体首次成功揭示了帕金森疾病在人类大脑细胞间扩散的分子机制，截止到现在，研究人员仅在实验动物体内观察到了帕金森疾病的扩散，而本文研究者首次在人类大脑中揭示了该疾病的扩散机制，相关研究刊登于国际杂志Neurobiology of Disease上。
文章中，研究者在人类大脑中发现了一种名为α-突触核蛋白的蛋白质，其在帕金森和痴呆症疾病患者大脑中会形成病理学修饰的蛋白形式，研究者Gabor G Kovacs表示，文章中我们首次揭示了人类神经细胞如何吸收这种病理学的α-突触核蛋白进而在细胞中互相转移（即扩散）。研究者首次利用了一种新型的抗体成功地区分了正常的α-突触核蛋白及疾病形式的α-突触核蛋白形式，这对于后期开发帕金森疾病的疗法将非常关键；Kovacs教授说道，对于帕金森患者来讲，病理性的α-突触核蛋白在不同脑细胞间的扩散机制为开发阻断疾病扩散转移的靶向疗法提供了新的思路，而在诊断学方面，这种新型抗体或许也是一种突破性的研究成果，其可以对个体是否患帕金森疾病进行早期的诊断。
最后研究者表示，这种新型抗体可以被用于对患者的脑脊髓液进行检测来确定病理性的α-突触核蛋白是否在患者大脑中，本文研究对于开发帕金森疾病的新型检测技术及靶向性疗法提供了新的希望和线索。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：
Intracellular processing of disease-associated α-synuclein in the human brain suggests prion-like cell-to-cell spread
Neurobiology of Disease DOI: 10.1016/j.nbd.2014.05.020
Gabor G. Kovacsa, , , Leonid Breydob, Ryan Greenb, Viktor Kisc, Gina Puskac, Péter Lőrinczc, Laura Perju-Dumbravaa, Regina Gieraa, Walter Pirkerd, Mirjam Lutza, Ingolf Lachmanne, Herbert Budkaa, 1, Vladimir N. Uverskyb, f, g, Kinga Molnárc, 2, Lajos Lászlóc
Dementia with Lewy bodies (DLB), Parkinson’s disease (PD) and multiple system atrophy are characterized by the deposition of disease-associated α-synuclein. In the present study we 1) examined the molecular specificity of the novel anti-α-synuclein 5G4 antibody; 2) evaluated immunoreactivity patterns and their correlation in human brain tissue with micro- and astrogliosis in 57 cases with PD or DLB; and 3) performed a systematic immunoelectron microscopical mapping of subcellular localizations. 5G4 strongly binds to the high molecular weight fraction of β-sheet rich oligomers, while no binding to primarily disordered oligomers or monomers was observed. We show novel localizations of disease-associated α-synuclein including perivascular macrophages, ependyma and cranial nerves. α-Synuclein immunoreactive neuropil dots and thin threads associate more with glial reaction than Lewy bodies alone. Astrocytic α-synuclein is an important component of the pathology. Furthermore, we document ultrastructurally the pathway of processing of disease-associated α-synuclein within neurons and astroglial cells. Interaction of mitochondria and disease-associated α-synuclein plays a key role in the molecular–structural cytopathogenesis of disorders with Lewy bodies. We conclude that 1) the 5G4 antibody has strong selectivity for β-sheet rich α-synuclein oligomers; 2) Lewy bodies themselves are not the most relevant morphological substrate that evokes tissue lesioning; 3) both neurons and astrocytes internalize disease-associated α-synuclein in the human brain, suggesting prion-like cell-to-cell spread of α-synuclein by uptake from surrounding structures, as shown previously in experimental observations.
Neurobiology of Disease DOI: 10.1016/j.nbd.2014.05.020
Gabor G. Kovacsa, , , Leonid Breydob, Ryan Greenb, Viktor Kisc, Gina Puskac, Péter Lőrinczc, Laura Perju-Dumbravaa, Regina Gieraa, Walter Pirkerd, Mirjam Lutza, Ingolf Lachmanne, Herbert Budkaa, 1, Vladimir N. Uverskyb, f, g, Kinga Molnárc, 2, Lajos Lászlóc
Dementia with Lewy bodies (DLB), Parkinson’s disease (PD) and multiple system atrophy are characterized by the deposition of disease-associated α-synuclein. In the present study we 1) examined the molecular specificity of the novel anti-α-synuclein 5G4 antibody; 2) evaluated immunoreactivity patterns and their correlation in human brain tissue with micro- and astrogliosis in 57 cases with PD or DLB; and 3) performed a systematic immunoelectron microscopical mapping of subcellular localizations. 5G4 strongly binds to the high molecular weight fraction of β-sheet rich oligomers, while no binding to primarily disordered oligomers or monomers was observed. We show novel localizations of disease-associated α-synuclein including perivascular macrophages, ependyma and cranial nerves. α-Synuclein immunoreactive neuropil dots and thin threads associate more with glial reaction than Lewy bodies alone. Astrocytic α-synuclein is an important component of the pathology. Furthermore, we document ultrastructurally the pathway of processing of disease-associated α-synuclein within neurons and astroglial cells. Interaction of mitochondria and disease-associated α-synuclein plays a key role in the molecular–structural cytopathogenesis of disorders with Lewy bodies. We conclude that 1) the 5G4 antibody has strong selectivity for β-sheet rich α-synuclein oligomers; 2) Lewy bodies themselves are not the most relevant morphological substrate that evokes tissue lesioning; 3) both neurons and astrocytes internalize disease-associated α-synuclein in the human brain, suggesting prion-like cell-to-cell spread of α-synuclein by uptake from surrounding structures, as shown previously in experimental observations.
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