Nicotine and Parkinsons - Nicotine Essay Example

Nicotine and Parkinsons

Parkinson’s disease  is a chronic  disorder where there is a  selective loss of dopaminergic neurons in the substantia nigra - Nicotine and Parkinsons introduction. In this disease  motor symptoms are treated by Levodopa and other dopaminergic agonists. The symptomatology for Parkinsons is  a presence of  gradually increasing resting tremor, bradykinesia, rigidity and postural instability. Recent advances in molecular biology have revealed that the pathogenesis of neuronal degeneration  may involve several molecular and cellular events, including oxidative stress, accumulation of toxic proteins resulting from dysfunction of the protein degradation system, proapoptotic mechanisms and mitochondrial dysfunction (von Bohlen und Halbach et al., 2004).

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It was suggested that a glial reaction and inflammatory processes may also participate in the cascade of events leading to neuronal degeneration in parkinsons. Lansgton et al. 1999  demonstrated the conspicuous presence of activated microglia in the Stria Nigra of patients with Parkinsons  who were exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which is known to be the most popular neurotoxin for the development of PD. Increased levels of cytokines such as tumour necrosis factor (TNF)-[alpha], interleukin-1[beta] and interferon  have been demonstrated. Inflammation has also been implicated in the neurodegenerative processes(Kelton, 2000) .

Role of nicotine

Nicotine is the major compound of tobacco. Recent epidemiological studies have confirmed that there is an inverse correlation between smoking and PD, and the effects of smoking are dose dependent. Experimentally, nicotine activates the striatal or mesolimbic dopaminergic system, and protects against glutamate-induced neurotoxicity in striatal, cortical and mesencephalic neurons, as well as nigrostriatal degeneration in MPTP-treated animals (Kelton, 2000)

The pathogenesis of the neuroprotective effect of nicotine against nigral dopaminergic neurons may be mediated by multiple mechanisms. Nicotine may play a direct neuroprotective role by modulating the monoamine oxidase activity, inhibiting complex I of the electron transport chain, acting as an antioxidant or stimulating drug-metabolizing enzymes in the cytochrome

Alternatively, nicotine could also act by stimulating nicotinic ACh receptors. Neuronal nicotinic ACh receptors are pentameric ligand-gated ion channels composed of [alpha] subunits or [alpha] and [beta] subunits, with six different [alpha] subunits ([alpha]2–[alpha]7) and three different [beta] subunits ([beta]2–[beta]4) expressed in the mammalian brain. and three different [beta] subunits ([beta]2–[beta]4) expressed in the mammalian brain (Gotti & Clementi, 2004). Of these nicotinic ACh receptors, [alpha]4 subtypes may have a role in nicotine-mediated protection against nigrostriatal injury by presynaptic and postsynaptic pathways. Nicotine significantly decreased the release of inflammatory cytokine and dopaminergic neuronal loss.

Research also suggests that Parkinson’s disease occurs less frequently in people who smoke or use other tobacco products, and that it is nicotine which is responsible for these positive effects. The number of nicotinic receptors are decreased in the brains of people who have Parkinson’s disease. The nicotine in cigarette smoke, in the nicotine patch or in gum may lead to an extra stimulation of these remaining nicotinic receptors (Kelton, 2000).

Referance

  1. Kelton MC, Kahn HJ, Conrath CL, Newhouse PA. The effects of nicotine on Parkinson’s disease. Brain Cogn. 2000 Jun-Aug;43(1-3):274-82.
  2. von Bohlen und Halbach, O., Schober, A. & Krieglstein, K. (2004) Genes, proteins, and neurotoxins involved in Parkinson’s disease. Prog. Neurobiol., 73, 151–177
  3. Gotti, C. & Clementi, F. (2004) Neuronal nicotinic receptors: from structure to pathology. Prog. Neurobiol., 74, 363–396.

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