Smoking and Parkinson's Disease: Does Nicotine Affect α-synuclein Fibrillation?
α-synuclein, Intrinsically Disordered Protein, Smoking, Parkinson's Disease, Nicotine, Hydroquinone, Fibrillation, Misfolding
Digital Object Identifier (DOI)
α-synuclein is a small presynaptic protein (14,460 D) that is abundantly distributed in the brain. Although, its function is unknown, the aggregated form of α-synuclein is a pathological hallmark of several neurodegenerative diseases, including Parkinson's disease (PD). Epidemiological studies have shown that smoking can lessen the incidence of Parkinson's disease, indicating that smoke may contain chemicals that are neuro-protective. The fibrillation of α-synuclein was studied in relation to five different compounds found in cigarette smoke: anabasine, cotinine, hydroquinone, nicotine and nornicotine. Thioflavin T assays, gel electrophoresis, size exclusion chromatography–high performance liquid chromatography (SEC–HPLC) and atomic force microscopy (AFM) were utilized to monitor the rate of α-synuclein fibrillation and the inhibitory effects of the cigarette smoke components. We show that nicotine and hydroquinone inhibit α-synuclein fibril formation in a concentration-dependent manner, with nicotine being more effective. The SEC–HPLC data show that nicotine and hydroquinone stabilize soluble oligomers. The morphology of the oligomers stabilized by nicotine was evaluated by AFM, which showed the presence of three stable oligomers with an average height of 16 nm, 10 nm and 4 nm. Comparable results were obtained for the effect of the cigarette smoke components on the A53T mutant fibrillation. These results show that nicotine and hydroquinone inhibit α-synuclein fibrillation and stabilize soluble oligomeric forms. This information can be used to understand the molecular mechanism of the nicotine and hydroquinone action to develop therapeutic solutions for PD.
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Citation / Publisher Attribution
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, v. 1794, issue 2, p. 282-290
Scholar Commons Citation
Hong, Dong-Pyo; Fink, Anthony L.; and Uversky, Vladimir N., "Smoking and Parkinson's Disease: Does Nicotine Affect α-synuclein Fibrillation?" (2009). Molecular Medicine Faculty Publications. 814.