α-Synuclein aggregation

被引:8
作者
Bodles, AM [1 ]
Irvine, GB
机构
[1] Univ Arkansas Med Sci, Donald W Reynolds Ctr Aging, Little Rock, AR 72205 USA
[2] Queens Univ Belfast, Sch Biol & Biochem, Ctr Med Biol, Peptide & Prot Res Grp, Belfast BT9 7BL, Antrim, North Ireland
关键词
alpha-synuclein; NAC; amyloid; aggregation; Parkinson's disease;
D O I
10.2174/0929866043407084
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 a major component of Lewy bodies in Parkinson's disease and is found associated with several other forms of dementia. As with other neurodegenerative diseases, the ability of alpha-synuclein to aggregate and form fibrillar deposits seems central to its pathology. We have defined a sequence within the NAC region of alpha-synuclein that is necessary for aggregation. Exploitation of chemically modified analogues of this peptide may produce inhibitors of aggregation..
引用
收藏
页码:271 / 279
页数:9
相关论文
共 46 条
[1]   Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system [J].
Abeliovich, A ;
Schmitz, Y ;
Fariñas, I ;
Choi-Lundberg, D ;
Ho, WH ;
Castillo, PE ;
Shinsky, N ;
Verdugo, JMG ;
Armanini, M ;
Ryan, A ;
Hynes, M ;
Phillips, H ;
Sulzer, D ;
Rosenthal, A .
NEURON, 2000, 25 (01) :239-252
[2]  
Baba M, 1998, AM J PATHOL, V152, P879
[3]   α-Synuclein accumulates in Lewy bodies in Parkinson's disease and dementia with Lewy bodies but not in Alzheimer's disease β-amyloid plaque cores [J].
Bayer, TA ;
Jäkälä, P ;
Hartmann, T ;
Havas, L ;
McLean, C ;
Culvenor, JG ;
Li, QX ;
Masters, CL ;
Falkai, P ;
Beyreuther, K .
NEUROSCIENCE LETTERS, 1999, 266 (03) :213-216
[4]   Inhibition of fibril formation and toxicity of a fragment of α-synuclein by an N-methylated peptide analogue [J].
Bodles, AM ;
El-Agnaf, OMA ;
Greer, B ;
Guthrie, DJS ;
Irvine, GB .
NEUROSCIENCE LETTERS, 2004, 359 (1-2) :89-93
[5]   Toxicity of non-Aβ component of Alzheimer's disease amyloid, and N-terminal fragments thereof, correlates to formation of β-sheet structure and fibrils [J].
Bodles, AM ;
Guthrie, DJS ;
Harriott, P ;
Campbell, P ;
Irvine, GB .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2000, 267 (08) :2186-2194
[6]   Identification of the region of non-Aβ component (NAC) of Alzheimer's disease amyloid responsible for its aggregation and toxicity [J].
Bodles, AM ;
Guthrie, DJS ;
Greer, B ;
Irvine, GB .
JOURNAL OF NEUROCHEMISTRY, 2001, 78 (02) :384-395
[7]  
Cabin DE, 2002, J NEUROSCI, V22, P8797
[8]   A broken α-helix in folded α-synuclein [J].
Chandra, S ;
Chen, XC ;
Rizo, J ;
Jahn, R ;
Südhof, TC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (17) :15313-15318
[9]   Kinetic stabilization of the α-synuclein protofibril by a dopamine-α-synuclein adduct [J].
Conway, KA ;
Rochet, JC ;
Bieganski, RM ;
Lansbury, PT .
SCIENCE, 2001, 294 (5545) :1346-1349
[10]   Non-Aβ component of Alzheimer's disease amyloid (NAC) revisited -: NAC and α-synuclein are not associated with Aβ amyloid [J].
Culvenor, JG ;
McLean, CA ;
Cutt, S ;
Campbell, BCV ;
Maher, F ;
Jäkälä, P ;
Hartmann, T ;
Beyreuther, K ;
Masters, CL ;
Li, QX .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 155 (04) :1173-1181