机构：[a]Department of Neural Plasticity, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan[b]Department of Neurobiology and Neurology, Xuanwu Hospital, Capital University of Medical Sciences, Beijing 100053, China神经内科首都医科大学宣武医院[c]Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan[d]RIKEN Harima Institute, 1-1-1 Kouto, Mikazuki-cho, Sayo-gun 679-5148, Japan[e]Electron Microscopy Center, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan[f]Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan[g]Department of Psychiatry and Pathology, NYU School of Medicine, New York, NY 10016, USA[h]Departments of Medicine and Neurology, UCLA School of Medicine, 16111 Plummer St., North Hills, CA 91343, USA[i]National Institute for Longevity Sciences, Morioka, Obu 474- 8522, Japan.
alpha-Synuclein is a major constituent of pathological intracellular inclusion bodies, a common feature of several neurodegenerative diseases. Two missense mutations in the alpha-synuclein gene have been identified in confirmed autosomal-dominant familial Parkinson's disease, which segregate with the illness. However, the physiological function of alpha-synuclein remains unknown. After biochemical investigations we have revealed tubulin to be an alpha-synuclein associated binding protein. Here, we show that a-synuclein induces polymerization of purified tubulin into microtubules. Mutant forms of alpha-synuclein lose this potential. The binding site of alpha-synuclein to tubulin is identified, and co-localization of alpha-synuclein with microtubules is shown in cultured cells. To our knowledge, this is the first demonstration of microtubule-polymerizing activity of alpha-synuclein. Now we can see a striking resemblance between alpha-synuclein and tau: both have the same physiological function and pathological features, making abnormal structures in diseased brains known as synucleinopathies and tauopathies. The discovery of a physiological role for alpha-synuclein may provide a new dimension in researches into the mechanisms of alpha-synuclein-associated neurodegenerative diseases.
基金：
grants from the Ministry of Education Science and Culture
of Japan, and Japan Society for the Promotion
of Science (to K.U.) and is supported by a fellowship
from the Science and Technology Agency of Japan (to
Q.L.M.).
第一作者机构：[a]Department of Neural Plasticity, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan[g]Department of Psychiatry and Pathology, NYU School of Medicine, New York, NY 10016, USA
通讯作者：
通讯机构：[a]Department of Neural Plasticity, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan
推荐引用方式(GB/T 7714)：
Muhammad Abdul Alim,Qiu-Lan Ma,Kazuya Takeda,et al.Demonstration of a role for alpha-synuclein as a functional microtubule-associated protein[J].JOURNAL OF ALZHEIMERS DISEASE.2004,6(4):435-442.doi:10.3233/JAD-2004-6412.
APA：
Muhammad Abdul Alim,Qiu-Lan Ma,Kazuya Takeda,Takako Aizawa,Mamoru Matsubara...&Kenji U′eda.(2004).Demonstration of a role for alpha-synuclein as a functional microtubule-associated protein.JOURNAL OF ALZHEIMERS DISEASE,6,(4)
MLA：
Muhammad Abdul Alim,et al."Demonstration of a role for alpha-synuclein as a functional microtubule-associated protein".JOURNAL OF ALZHEIMERS DISEASE 6..4(2004):435-442
