3, 4-Dihydroxyphenylacetic Acid (DOPAC) Impairs α-Synuclein Interaction with Lipids
| Autor: | Wenbo Zhou, Anthony L. Fink, Chunmei Long, Vladimir N. Uversky |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Fibrillation
3 4-Dihydroxyphenylacetic acid Parkinson's disease animal diseases Biochemistry (medical) Clinical Biochemistry medicine.disease Biochemistry In vitro nervous system diseases chemistry.chemical_compound Fibril formation nervous system chemistry Mole health occupations medicine heterocyclic compounds α synuclein medicine.symptom Dopamine metabolism |
| Zdroj: | The Open Proteomics Journal. 3:1-7 |
| ISSN: | 1875-0397 |
| DOI: | 10.2174/1875039701003010001 |
| Popis: | α-Synuclein (α-Syn) is a small intrinsically disordered presynaptic protein known to form insoluble filamen- tous 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. |
| Databáze: | OpenAIRE |
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