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PMID: 19013262 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Smoking and Parkinson's disease: does nicotine affect alpha-synuclein fibrillation?

Biochimica et biophysica acta ·Vol. 1794 ·No. 2 ·2009-02-00 ·Pages 282-90

Hong DP, Fink AL, Uversky VN

Abstract

alpha-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 alpha-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 alpha-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 alpha-synuclein fibrillation and the inhibitory effects of the cigarette smoke components. We show that nicotine and hydroquinone inhibit alpha-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 alpha-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.

MeSH Terms
Amino Acid Sequence Anabasine/pharmacology Benzothiazoles Chromatography, Gel Cotinine/pharmacology Humans Hydroquinones/pharmacology Microscopy, Atomic Force Molecular Sequence Data Mutation Nicotine/analogs & derivatives,pharmacology Parkinson Disease/metabolism Protein Binding Protein Multimerization Smoking/adverse effects Thiazoles/metabolism alpha-Synuclein/genetics,metabolism,ultrastructure
Chemicals
Benzothiazoles Hydroquinones Thiazoles alpha-Synuclein thioflavin T Nicotine nornicotine Cotinine Anabasine hydroquinone
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hong Dong-Pyo
Department of Chemistry and Biochemistry, University of California at Santa Cruz, Santa Cruz, California 95064, USA.
Fink Anthony L
Uversky Vladimir N
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Article Info
Journal
Biochimica et biophysica acta
Abbr.
Biochim Biophys Acta
ISSN
0006-3002
DOI
10.1016/j.bbapap.2008.09.026
Published
2009-02-00
Epub
2008-00-25
Pages
282-90
Language
English
Region
Netherlands
NLM ID
0217513
PMCID
PMC2647853
Subset
IM
Grants
NINDS NIH HHS · R01 NS39985 · United States
NLM NIH HHS · R01 LM007688-01A1 · United States
NINDS NIH HHS · R01 NS039985-03 · United States
NLM NIH HHS · R01 LM007688 · United States
NIGMS NIH HHS · R01 GM071714 · United States
NIGMS NIH HHS · R01 GM071714-01A2 · United States
External Links
PubMed source DOI: 10.1016/j.bbapap.2008.09.026 PMC Full Text
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