The Strange Relationship between Nicotine and Parkinson’s Disease

According to the World Health Organization, smoking is responsible for approximately 6 million deaths in the world every year or one fatality every six seconds.  71% of all lung cancers and 42% of all chronic obstructive pulmonary diseases are attributable to tobacco use.  Oddly enough, not everything related to smoking is bad news: smokers seem to be protected against Parkinson’s disease.  Studies have shown that people who smoke on a regular basis are about two-fold less likely to suffer from Parkinson’s disease.  A similar relationship exists between Parkinson’s and coffee.  Nicotine and caffeine, both alkaloid chemicals, are stimulants which act on the sympathetic nervous system.  The mechanism of protection against Parkinson’s disease is unknown in both cases; unveiling it would help both to increase the understanding of the disease and to develop strategies to treat it.  Recent work published in the Journal of Neuroscience by Henry Lester and his team at Caltech sheds some light on the relationship between nicotine and Parkinson’s.

Brain Cigarette Knowing Neurons

Parkinson’s disease is a neurodegenerative disease characterized by a resting tremor (an unintentional, rhythmic movement when the muscle is relaxed, most often in the hands).  It is also characterized by rigidity in the muscles, which can be associated with pain, bradykinesia (slowness of movement), and postural instability.  The origin of these effects seems to lie in the selective loss of a population of neurons that produce a neurotransmitter called dopamine.  Aside from being involved in the reward pathway, dopamine is also critically involved in a brain circuit known as the nigrostriatal pathway, which is involved in the production of movement.  When dopaminergic neurons in this pathway die, as in Parkinson’s disease, patients are left with the debilitating motor control issues mentioned above.

Nigrostriatal Pathway Knowing Neurons

Although the causes of neuronal cell death are not well understood, aggregates (or clusters) of misfolded proteins are commonly found inside diseased cells.  In a healthy cell, as much as one third of the proteins synthesized by the cell fail to fold correctly and require the intervention of a set of proteins called chaperones, which attempt to refold them.  If they fail, the misfolded proteins are eventually eliminated from the system.  In diseased cells observed in like Parkinson’s, misfolded proteins accumulate and aggregate, disrupting the normal function of the cell, eventually leading to its death.

KN Parkinsons Folding ProtienEdit2

So how might nicotine be protecting cells from dying in people with Parkinson’s disease?  To answer this question, Dr. Lester and his team studied the effect of nicotine on dopaminergic neurons over time.  To simulate the conditions that drive protein aggregation in dopaminergic neurons from Parkinson’s patients, the authors used a drug called tunycamycin, which affects normal protein folding.  This response not only increases chaperone levels (which try to refold the misfolded proteins), but eventually activates proteins that promote cell death.  The authors observed that in the presence of nicotine, the dopaminergic neurons were better able to counteract the toxic effects triggered by protein misfolding.  Moreover, even blocking nicotine receptors did not alter this observation.

How is this possible?  The authors hypothesize that nicotine permeates the plasma membrane and acts as a pharmacological chaperone inside the cell, reducing protein misfolding and protecting the cells against the formation of aggregates.  Further work is needed to confirm this hypothesis, but the results open up the possibility of developing nicotine-based therapies that circumvent the obvious health problems associated with smoking.

There is, however, a better way to prevent Parkinson’s that will save you the trouble of cancer, lung disease, and bad breath: exercise!  Exercise reduces your risk for Parkinson’s disease and many other pathologies, suggesting you might be better off spending your money on running shoes rather than in cigarettes.  And even if you develop Parkinson’s disease, smoking tobacco is never medically justifiable.  For this reason, researchers are working hard to isolate nicotine’s protective effects from the act of smoking per se to develop much needed treatments for patients with this debilitating disease.


Written by Ignacio Amigo.

Images by David Jaimes and Jooyeun Lee.



Srinivasan R, Henley BM, Henderson BJ, Indersmitten T, Cohen BN, Kim CH, McKinney S, Deshpande P, Xiao C, and Lester HA. (2016) Smoking-Relevant Nicotine Concentration Attenuates the Unfolded Protein Response in Dopaminergic Neurons. Journal of Neuroscience 36(1):65-79. DOI:


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4 thoughts on “The Strange Relationship between Nicotine and Parkinson’s Disease

  • May 25, 2016 at 2:58 pm

    My name Douglas Christmann from England, Oxford,UK …Parkinson disease has been ongoing in my family for long..I lost both parents to Parkinson and it is so much pain have not been able to get over. As we all know medically,there is no solution or cure for Parkinson disease and the cost for Medication is very expensive..Someone introduced me to a herbal doctor(Native Medical Practitioner)in oxford..I showed the man all my Tests and Results and i told him i have already diagnosed with Parkinson disease and i have spent thousands of dollars on medication..I said i will like to try him cos someone introduced me to him..He asked me sorts of questions and i answered him correctly..To cut the story short,He gave me some medicinal soaps and some herbs(i have forgot the name he called them) and he thought me how am gonna use them all..At first i was skeptical but i just gave it a try..I was on his Medication for 2 weeks and i used all the soaps and herbs according to his prescription.. that he will finish the rest himself..and i called him 3 days after, i arrived and i told him what is the next thing..he said,he has been expecting my call.. he told me to visit my doctor for another test..Honestly speaking, i never believe all he was saying until after the test when my doctor mention the statement that am Parkinson disease negative and the doctor started asking me how do i do it….If you are out there suffering from this deadly disease you can also contact him via email:, i believe he can also be of help to you.

  • February 27, 2018 at 8:13 pm

    It says they are trying isolate nicotine in a safe way. Haven’t they already done this with nicotine gum and patches?

  • May 30, 2018 at 7:30 am

    Joseph, they mean isolating the one part of nicotine that has this neuroprotective effect. Even though nicotine is just as safe as coffee and not addictive by itself. It’s become a trigger word for the general public because nicotine is in cigarettes. I also commonly hear people refer to being addicted to the nicotine in cigarettes which is simply not true. Tobacco is addicting.

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