一項(xiàng)韓,、美共同研究提出了神經(jīng)退行性疾病病情進(jìn)展機(jī)理的新理論,，有助于找到更有效地治療帕金森氏癥和阿爾茨海默氏癥等老年神經(jīng)性疾病的新方法。
韓國《聯(lián)合新聞》網(wǎng)站報(bào)道說,，韓國建國大學(xué)生命科學(xué)系教授李承載領(lǐng)導(dǎo)的韓國研究團(tuán)隊(duì)和美國研究機(jī)構(gòu)的一項(xiàng)共同研究發(fā)現(xiàn),，受損的神經(jīng)細(xì)胞能夠?qū)е录?xì)胞內(nèi)的α突觸核蛋白聚合體在神經(jīng)細(xì)胞之間傳遞，進(jìn)而誘發(fā)周圍神經(jīng)細(xì)胞內(nèi)正常蛋白質(zhì)的變異,。這一過程被認(rèn)為同神經(jīng)退行性疾病病情進(jìn)展的過程高度相關(guān),。
這項(xiàng)研究成果本月28日發(fā)表在美國《國家科學(xué)院院刊》網(wǎng)絡(luò)版上。
韓國研究團(tuán)隊(duì)不久前在韓國學(xué)術(shù)刊物上發(fā)表的相關(guān)論文指出,，α突觸核蛋白聚合體以低聚體,、原纖維等多種形態(tài)存在?；蛲蛔兗铀倭?alpha;突觸核蛋白形成聚合體的過程,。由于低聚體形式的α突觸核蛋白聚合體表現(xiàn)出多種細(xì)胞毒性，所以能夠觸發(fā)多種細(xì)胞防御機(jī)制,。此次研究發(fā)現(xiàn),，在這種機(jī)制的作用下,，部分α突觸核蛋白低聚體被移動到一種泡囊中并分泌出細(xì)胞外,。
研究人員認(rèn)為，更完善的蛋白質(zhì)變異檢測技術(shù)和阻斷變異蛋白質(zhì)向周圍細(xì)胞移動的技術(shù)有望成為診斷和治療退行性腦部疾患的另一個(gè)開發(fā)方向,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
