Cigarette Smoking, Nicotine and Parkinson’s Disease

Parkinson’s disease is a movement disorder which occurs in about 1% of the general population above 55 years of age. It manifests as selective damage to the dopaminergic neurons, which are situated in the nigro-striatal region of the brain and leads to motor-deficits which includes rigidity, tremors, dementia, frequent falls, and freezing of gait in the later stages.

Dopamine replacement therapy is the most commonly used treatment strategy against PD. However it provides only symptomatic relief and the disease progresses inevitably. Also, as the time goes by, it loses its efficacy along with a substantial increase in the side effects. That being said, it becomes crucial to develop an interventional strategy, which can effectively retard, halt or even reverse the process of disease progression. In this regard, the epidemiological studies over the past 50 years have shown a lower incidence of Parkinson’s disease among cigarette smokers. This finding forms an important cornerstone and provides crucial evidences about the therapeutic strategies for Parkinson’s disease.

It is believed that Nicotine stimulates the dopaminergic receptors in the brain which are evidently destroyed in Parkinson’s disease. The study is crucial to develop interventional strategies to retard or halt the disease progression.The main concern was whether this epidemiological finding was just a coincidence, which although unlikely, had not been clinically verified until the recent years. A new research study conducted at Institut du Cerveau et de la Moelle Épinière, Hôpital de la Salpêtrière, in Paris, France has confirmed the potential benefit of nicotine in Parkinson’s disease by its action on a specific type of receptor on neurons.

Moreover, the beneficial association of cigarette smoking with Parkinson’s disease has been independently studied in 40 different experimental models by different investigators conducted over the past 50 years. Although this apparent neuro-protective benefit of cigarette smoking has been known for a while, be it due to nicotine or the scores of other chemicals in cigarettes, the mechanism has been poorly understood and the therapeutic implications yet to be taken advantage of in the development of new Parkinson’s disease drugs.

Nicotine Effect on Dopamine Release

Nicotine, whether on its own or with other monoamine oxidase inhibitors and yet undiscovered chemicals in cigarette smoke, stimulates the dopaminergic neurons in the brain. It can exert either non-receptor mediated biological effect or can act independently on the various nicotinic receptor sub types located in the nigro-striatal region of the brain which are predominantly affected due to the dopaminergic loss caused in Parkinson’s disease. Current PD susceptible smokers are sixty percent less likely to develop the disease as compared to the susceptible non smokers.

It offers true protective effects against Pd. It not only slows the disease progression, but also delays the onset or occurrence of disease in healthy but genetically susceptible individuals. The beneficial effect of smoking is dose dependent and relates to the number of cigarette-pack-years.

Although previous studies did indicate that the damage to the substantia nigra, the area of the brain most affected in Parkinson’s disease, was limited with nicotine and exacerbated by pesticides and toxins, the exact mechanism and receptor sites for this neuroprotective effect of nicotine were not conclusively verified. It was believed to be those same receptors, alpha-7 nicotine receptors, as was verified by the recent study. These previous studies also put forward the idea that other non-receptor mediated mechanisms may offer protection by suppressing the effect of toxins and altering the activity of the enzyme monoamine oxidase.

Nicotine Receptors on Dopamine Nerves

There is a presence of specific nicotinic acetyl choline recptors (nACh receptors) in the nigro-striatal region of the brain, and it has various receptor sub types. Nicotine exerts its effects by stimulating these nACh receptors in the peripheral as well as central nervous system.

In the recent study conducted in France, it was found that nicotine spares the gradual loss of these neurons by acting on alpha-7 nicotine receptors. Mice that were genetically engineered without these receptors were shown to be more likely to lose dopaminergic neurons than normal mice with these receptors. These findings were recently published in the FASEB journal (August 2011) and go a long way in opening up possibilities of new drugs that target the alpha-7 nicotine receptors. New generation drugs may be able to prevent Parkinson’s disease in high risk individuals or slow the progression of the disease.

Smoking Benefit in Parkinson’s Disease

The findings of the recent study are promising and offers new hope for Parkinson’s disease like the recent VPS35 genetic mutation discovery which sheds new light on familial Parkinson’s disease.

Nicotine and nicotine agonists that selectively stimulate nACh receptors, have a modulatory effect and enhances the release of dopamine from nigro-striatal neurons in the patients of parkinsonism. It gradually relieves the motor symptoms and provides a long term protection against the nigro-striatal damage. In this way, it also reduces the disease progression. Hence, nicotine can be successfully used as an adjunct therapy along with L- Levodopa for parkinsonism patients.

The dopamine-producing nerve cells are progressively destroyed in Parkinson’s disease and dopamine is supplemented with the aid of medication like L-dopa. However, the drawback with L-dopa is the side effects and an attempt to reduce the dose only worsens the symptoms.

This adjunction also allows for the dose reduction of L-Levodopa and thereby combats the unwanted side effects. It is found to reduce the L-dopa induced dyskinetic like movements (abnormal involuntary movements), which is a serious side effect following its chronic treatment. These side effects are gravely debilitating and have an adverse effect on the patient’s quality of life. Although, it must also be kept in mind that nicotine is proved to be neuroprotective but is not found to be neurorestorative in experimental studies carried out in mice and monkeys.
However, this should not encourage every PD patient to take up cigarette smoking. The host of carcinogens (cancer-causing chemicals) in cigarette smoke may be a greater risk to one’s health and lifespan, along with the known cardiovascular implications of cigarette smoking. Having said that, the potential therapeutic uses of nicotine patches and nicotine chewing gums must be taken into account and are too intriguing to ignore. Nevertheless, the finding does open up some exciting avenues for future development of drugs that can take advantage of the neuroprotective effect of nicotine by now identifying the specific receptors responsible for this benefit.

1 Comment

  1. I wondered if passive smoking has the same effect, as my partner who lives next doom to me is a heavy smoker even though he doesn’t smoke when I’m in there.

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