Interactions between metals and α-synuclein -: function or artefact?

被引:44
作者
Brown, David R. [1 ]
机构
[1] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England
关键词
amyloid; copper; Lewy body; Parkinson's disease;
D O I
10.1111/j.1742-4658.2007.05917.x
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
alpha-synuclein is one of a family of proteins whose function remains unknown. This protein has become linked to a number of neurodegenerative disease although its potential causative role in these diseases remains mysterious. In diseases such as Parkinson's disease and Lewy body dementias, alpha-synuclein becomes deposited in aggregates termed Lewy bodies. Also, some inherited forms of Parkinson's diseases are linked to mutations in the gene for alpha-synuclein. Studies have mostly focussed on what causes the aggregation of the protein but, like many amyloidogenic proteins associated with a neurodegenerative disorder, this protein has now been suggested to bind copper. This finding is currently controversial. This review examines the evidence that alpha-synuclein is a copper binding protein and discusses whether this has any significance in determining the function of the protein or whether copper binding is at all necessary for aggregation.
引用
收藏
页码:3766 / 3774
页数:9
相关论文
共 80 条
[41]   Subcellular localization of wild-type and Parkinson's disease-associated mutant α-synuclein in human and transgenic mouse brain [J].
Kahle, PJ ;
Neumann, M ;
Ozmen, L ;
Müller, V ;
Jacobsen, H ;
Schindzielorz, A ;
Okochi, M ;
Leimer, U ;
van der Putten, H ;
Probst, A ;
Kremmer, E ;
Kretzschmar, HA ;
Haass, C .
JOURNAL OF NEUROSCIENCE, 2000, 20 (17) :6365-6373
[42]   Detection of novel intracellular α-synuclein oligomeric species by fluorescence lifetime imaging [J].
Klucken, Jochen ;
Outeiro, Tiago F. ;
Nguyen, Paul ;
McLean, Pamela J. ;
Hyman, Bradley T. .
FASEB JOURNAL, 2006, 20 (12) :2050-2057
[43]   Coordination abilities of N-terminal fragments of α-synuclein towards copper(II) ions:: A combined potentiometric and spectroscopic study [J].
Kowalik-Jankowska, T ;
Rajewska, A ;
Wisniewska, K ;
Grzonka, Z ;
Jezierska, J .
JOURNAL OF INORGANIC BIOCHEMISTRY, 2005, 99 (12) :2282-2291
[44]   Copper(II) binding by fragments of α-synuclein containing M1-D2- and -H50-residues;: a combined potentiometric and spectroscopic study [J].
Kowalik-Jankowska, Teresa ;
Rajewska, Anna ;
Jankowska, Elzbieta ;
Grzonka, Zbigniew .
DALTON TRANSACTIONS, 2006, 42 (42) :5068-5076
[45]   Products of Cu(II)-catalyzed oxidation of the N-terminal fragments of α-synuclein in the presence of hydrogen peroxide [J].
Kowalik-Jankowska, Teresa ;
Rajewska, Anna ;
Jankowska, Elzbieta ;
Wisniewska, Kornelia ;
Grzonka, Zbigniew .
JOURNAL OF INORGANIC BIOCHEMISTRY, 2006, 100 (10) :1623-1631
[46]   Presynaptic α-synuclein aggregates, not Lewy bodies, cause neurodegeneration in dementia with Lewy bodies [J].
Kramer, Michael L. ;
Schulz-Schaeffer, Walter J. .
JOURNAL OF NEUROSCIENCE, 2007, 27 (06) :1405-1410
[47]   Ala30Pro mutation in the gene encoding α-synuclein in Parkinson's disease [J].
Krüger, R ;
Kuhn, W ;
Müller, T ;
Woitalla, D ;
Graeber, M ;
Kösel, S ;
Przuntek, H ;
Epplen, JT ;
Schöls, L ;
Riess, O .
NATURE GENETICS, 1998, 18 (02) :106-108
[48]   Novel α-synuclein-immunoreactive proteins in brain samples from the Contursi kindred, Parkinson's, and Alzheimer's disease [J].
Langston, JW ;
Sastry, S ;
Chan, P ;
Forno, LS ;
Bolin, LM ;
Di Monte, DA .
EXPERIMENTAL NEUROLOGY, 1998, 154 (02) :684-690
[49]   Lipid interaction of α-synuclein during the metal-catalyzed oxidation in the presence of Cu2+ and H2O2 [J].
Lee, EN ;
Lee, SY ;
Lee, D ;
Kim, J ;
Paik, SR .
JOURNAL OF NEUROCHEMISTRY, 2003, 84 (05) :1128-1142
[50]   Human α-synuclein-harboring familial Parkinson's disease-linked Ala-53→Thr mutation causes neurodegenerative disease with α-synuclein aggregation in transgenic mice [J].
Lee, MK ;
Stirling, W ;
Xu, YQ ;
Xu, XY ;
Qui, D ;
Mandir, AS ;
Dawson, TM ;
Copeland, NG ;
Jenkins, NA ;
Price, DL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (13) :8968-8973