一项韩、美共同研究提出了神经退行性疾病病情进展机理的新理论，有助于找到更有效地治疗帕金森氏症和阿尔茨海默氏症等老年神经性疾病的新方法。
韩国《联合新闻》网站报道说，韩国建国大学生命科学系教授李承载领导的韩国研究团队和美国研究机构的一项共同研究发现，受损的神经细胞能够导致细胞内的α突触核蛋白聚合体在神经细胞之间传递，进而诱发周围神经细胞内正常蛋白质的变异。这一过程被认为同神经退行性疾病病情进展的过程高度相关。
这项研究成果本月28日发表在美国《国家科学院院刊》网络版上。
韩国研究团队不久前在韩国学术刊物上发表的相关论文指出，α突触核蛋白聚合体以低聚体、原纤维等多种形态存在。基因突变加速了α突触核蛋白形成聚合体的过程。由于低聚体形式的α突触核蛋白聚合体表现出多种细胞毒性，所以能够触发多种细胞防御机制。此次研究发现，在这种机制的作用下，部分α突触核蛋白低聚体被移动到一种泡囊中并分泌出细胞外。
研究人员认为，更完善的蛋白质变异检测技术和阻断变异蛋白质向周围细胞移动的技术有望成为诊断和治疗退行性脑部疾患的另一个开发方向。（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS July 27, 2009, doi: 10.1073/pnas.0903691106
Inclusion formation and neuronal cell death through neuron-to-neuron transmission of α-synuclein
Paula Desplatsa,1, He-Jin Leeb,c,1, Eun-Jin Baeb, Christina Patricka, Edward Rockensteina, Leslie Crewsa, Brian Spencera, Eliezer Masliaha,2 and Seung-Jae Leeb,2
aDepartment of Neurosciences and Pathology, School of Medicine, University of California at San Diego, La Jolla, CA 92093; and
bDepartment of Biomedical Science and Technology, Institute of Biomedical Science and Technology, and
cDepartment of Anatomy, School of Medicine, BK21, Konkuk University, Seoul 143-701, South Korea
Neuronal accumulation of α-synuclein and Lewy body formation are characteristic to many neurodegenerative diseases, including Parkinson's disease (PD). This Lewy pathology appears to spread throughout the brain as the disease progresses. Furthermore, recent studies showed the occurrence of Lewy pathology in neurons grafted into the brains of PD patients, suggesting the spread of pathology from the host tissues to the grafts. The mechanism underlying this propagation is unknown. Here, we show that α-synuclein is transmitted via endocytosis to neighboring neurons and neuronal precursor cells, forming Lewy-like inclusions. Moreover, α-synuclein was transmitted from the affected neurons to engrafted neuronal precursor cells in a transgenic model of PD-like pathology. Failure of the protein quality control systems, especially lysosomes, promoted the accumulation of transmitted α-synuclein and inclusion formation. Cells exposed to neuron-derived α-synuclein showed signs of apoptosis, such as nuclear fragmentation and caspase 3 activation, both in vitro and in vivo. These findings demonstrate the cell-to-cell transmission of α-synuclein aggregates and provide critical insights into the mechanism of pathological progression in PD and other proteinopathies.
