TY - JOUR
T1 - 3, 4-Dihydroxyphenylacetic Acid (DOPAC) impairs α-synuclein interaction with lipids
AU - Zhou, Wenbo
AU - Long, Chunmei
AU - Fink, Anthony L.
AU - Uversky, Vladimir N.
PY - 2010/2/4
Y1 - 2010/2/4
N2 - α-Synuclein (α-Syn) is a small intrinsically disordered presynaptic protein known to form insoluble filamentous inclusions in Parkinson's disease (PD) and other neurodegenerative disorders. Various catecholamines can inhibit the α-Syn fibrillation in vitro. Recently, non-covalent binding of DOPAC (3,4-dihydroxyphenylacetic acid), a normal product of the dopamine metabolism, was shown to inhibit the fibrillation of α-Syn due to the DOPAC-induced stabilization of the normally transient oligomers thus preventing them from subsequent fibril formation (Zhou, et al. J. Mol. Biol. 2009, 388 (3), 597-610). We are showing here that the interaction of DOPAC with α-Syn decreases the binding affinity of α-Syn to lipids, suggesting that DOPAC might lead to the gain-of-toxicity of α-Syn aggregates and loss-of-function of α-Syn, both of which could be related to progression of PD.
AB - α-Synuclein (α-Syn) is a small intrinsically disordered presynaptic protein known to form insoluble filamentous inclusions in Parkinson's disease (PD) and other neurodegenerative disorders. Various catecholamines can inhibit the α-Syn fibrillation in vitro. Recently, non-covalent binding of DOPAC (3,4-dihydroxyphenylacetic acid), a normal product of the dopamine metabolism, was shown to inhibit the fibrillation of α-Syn due to the DOPAC-induced stabilization of the normally transient oligomers thus preventing them from subsequent fibril formation (Zhou, et al. J. Mol. Biol. 2009, 388 (3), 597-610). We are showing here that the interaction of DOPAC with α-Syn decreases the binding affinity of α-Syn to lipids, suggesting that DOPAC might lead to the gain-of-toxicity of α-Syn aggregates and loss-of-function of α-Syn, both of which could be related to progression of PD.
KW - α-synuclein
KW - Aggregation
KW - Intrinsically disordered protein
KW - Oligomerization
KW - Parkinson's disease
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UR - http://www.scopus.com/inward/citedby.url?scp=77953390471&partnerID=8YFLogxK
U2 - 10.2174/1875039701003010001
DO - 10.2174/1875039701003010001
M3 - Article
AN - SCOPUS:77953390471
SN - 1875-0397
VL - 3
SP - 1
EP - 7
JO - Open Proteomics Journal
JF - Open Proteomics Journal
ER -