Abstract

Strong epidemiologic evidence suggests that smokers and coffee drinkers have a lower risk of Parkinson's disease (PD). The explanation for this finding is still unknown, and the discussion has focused on two main hypotheses. The first suggests that PD patients have premorbid personality traits associated with dislike for coffee-drinking and smoking. The second posits that caffeine and nicotine are neuroprotective. We propose an alternative third hypothesis, in which both cigarette and coffee consumption change the composition of the microbiota in the gut in a way that mitigates intestinal inflammation. This, in turn, would lead to less misfolding of the protein alpha-synuclein in enteric nerves, reducing the risk of PD by minimizing propagation of the protein aggregates to the central nervous system, where they otherwise can induce neurodegeneration. © 2014 International Parkinson and Movement Disorder Society.

© 2014 International Parkinson and Movement Disorder Society.

http://www.ncbi.nlm.nih.gov/pubmed/24753353

Alpha-synuclein misfolding is a leading contender for the cause of PD. So, anything which enables the measurement of the misfolding process is to be welcomed.

Nanopore analysis is a quick way of discovering drugs which help to reduce alpha-synuclein misfolding. "Nanopore analysis is an emerging technique that enables the investigation of the conformation of a single peptide or protein molecule. Briefly, a pore is inserted into a membrane under voltage clamp conditions. When a molecule interacts with the pore there is a change in the current, I, for a time, T." [1]

Using this technique, researchers at the University of Saskatchewan, Canada, have shown that both nicotine and caffeine bind to alpha-synuclein, reducing misfolding. The use of both drugs may have an effect that is much larger than either one on its own [2].

References

[1] Prion. 2012 Apr-Jun;6(2):116-23. doi: 10.4161/pri.18665. Epub 2012 Apr 1.
"Nanopore analysis: An emerging technique for studying the folding and misfolding of proteins."
Madampage C, Tavassoly O, Christensen C, Kumari M, Lee JS.
http://www.ncbi.nlm.nih.gov/pubmed/22421211

[2] "Caffeine, nicotine may help hinder disease"
Jonathan Charlton, The Starphoenix
Published: Wednesday, April 09, 2014
http://www2.canada.com/reginaleaderp...5-496af9fa5804

John