Residual substantia nigra neuromelanin in Parkinson's disease is cross-linked to α-synuclein

被引:58
作者
Fasano, M
Giraudo, S
Coha, S
Bergamasco, B
Lopiano, L
机构
[1] Univ Insubria, Dept Struct & Funct Biol, I-21100 Varese, Italy
[2] Univ Turin, Dept Neurosci, I-10126 Turin, Italy
[3] IRCCS, Salvatore Maugeri Fdn, I-27100 Pavia, Italy
关键词
alpha-synuclein; Lewy bodies; neuromelanin; Parkinson's disease; Western blotting;
D O I
10.1016/S0197-0186(02)00161-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The pigmentation of substantia nigra pars compacta dopaminergic neurons is due to the presence of neuromelanin, an irregular macromolecular pigment belonging to the family of melanins. Depletion of neuromelanin in Parkinson's disease is typically indicated by loss of brown color in this area. Unlike that from controls, the pigment extracted from substantia nigra of parkinsonian patients seems to be mainly composed by highly cross-linked, protease-resistant proteic material and the neuromelanin macromolecule appears to be a minor presence. In the present paper we describe the isolation by SDS-PAGE of this proteic component after cleavage of the melanin backbone under solubilizing conditions. A single band is observed, which has been identified as et-synuclein by western blotting. As expected, the same process performed on a control specimen did not show occurrence of any major proteic component. Nevertheless, extraction from a 91 years old control with Lewy bodies displayed minor alpha-synuclein immunoreactive aggregates, whereas inclusion of free alpha-synuclein was not observed at all. Results reported here support the view that alpha-synuclein accumulates within substantia nigra neurons and is entrapped in pigment granules during neuromelanin biosynthesis, i.e. before the melanin depletion characteristic of Parkinson's disease starts. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:603 / 606
页数:4
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