α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies

Proceedings of the National Academy of Sciences of the United States of America - Tập 95 Số 11 - Trang 6469-6473 - 1998
Maria Grazia Spillantini1, R. Anthony Crowther1, Ross Jakes1, Masato Hasegawa1, Michel Goedert1
1Medical Research Council Centre for Brain Repair and Department of Neurology, University of Cambridge, Robinson Way, Cambridge CB2 2PY, United Kingdom; and Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom

Tóm tắt

Lewy bodies and Lewy neurites are the defining neuropathological characteristics of Parkinson’s disease and dementia with Lewy bodies. They are made of abnormal filamentous assemblies of unknown composition. We show here that Lewy bodies and Lewy neurites from Parkinson’s disease and dementia with Lewy bodies are stained strongly by antibodies directed against amino-terminal and carboxyl-terminal sequences of α-synuclein, showing the presence of full-length or close to full-length α-synuclein. The number of α-synuclein-stained structures exceeded that immunoreactive for ubiquitin, which is currently the most sensitive marker of Lewy bodies and Lewy neurites. Staining for α-synuclein thus will replace staining for ubiquitin as the preferred method for detecting Lewy bodies and Lewy neurites. We have isolated Lewy body filaments by a method used for the extraction of paired helical filaments from Alzheimer’s disease brain. By immunoelectron microscopy, extracted filaments were labeled strongly by anti-α-synuclein antibodies. The morphologies of the 5- to 10-nm filaments and their staining characteristics suggest that extended α-synuclein molecules run parallel to the filament axis and that the filaments are polar structures. These findings indicate that α-synuclein forms the major filamentous component of Lewy bodies and Lewy neurites.

Từ khóa


Tài liệu tham khảo

F H Lewy Handbuch der Neurologie 3 , 920–933 (1912).

M C Trétiakoff Ph.D. thesis (University of Paris, 1919).

10.1097/00005072-199603000-00001

10.1097/00005072-196507000-00003

10.1002/path.1710990106

10.1097/00005072-196104000-00007

10.1007/BF00685366

10.1111/j.1750-3639.1998.tb00156.x

10.1212/WNL.41.9.1402

10.1126/science.6308771

M L Schmidt, J Murray, V M-Y Lee, W D Hill, A Wertkin, J Q Trojanowski Am J Pathol 139, 53–65 (1991).

10.1097/00005072-199305000-00001

10.1007/BF00687787

10.1002/path.1711550105

10.1073/pnas.85.12.4501

10.1126/science.276.5321.2045

10.1038/ng0298-106

10.1038/42166

10.1016/0014-5793(94)00395-5

H Ji, J E Liu, T Jia, M Wang, J Liu, G Xiao, B K Joseph, C Rosen, Y E Shi Cancer Res 57, 759–764 (1997).

10.1073/pnas.85.8.2854

10.1073/pnas.87.10.3947

10.1073/pnas.87.15.5827

10.1016/0896-6273(92)90117-V

10.1073/pnas.88.6.2288

10.1016/S0304-3940(97)00891-4

A Takeda, M Mallory, M Sundsmo, W Honer, L Hansen, E Masliah Am J Pathol 152, 367–372 (1998).

10.1007/BF00688674

10.1093/brain/110.5.1131

10.1007/BF00687767

P G Galloway, P Mulvihill, G Perry Am J Pathol 140, 809–822 (1992).

T Iwatsubo, H Yamaguchi, M Fujimoro, H Yokosawa, Y Ihara, J Q Trojanowski, V M-Y Lee Am J Pathol 148, 1517–1529 (1996).

10.1021/bi961799n

10.1002/j.1460-2075.1985.tb04132.x

10.1006/jmbi.1996.0322

10.1016/0896-6273(89)90210-9

Thông tin
Thông tin xuất bản

Proceedings of the National Academy of Sciences of the United States of America

Tập 95 Số 11

6469-6473

Thông tin tác giả