Parkinsons disease

Parkinson’s Disease and the protective mechanism of the antioxidant Vitamin EDescription and RisksParkinson’s disease (PD) is a progressive movement disorder marked by tremors, rigidity, slow movements (bradykinesia), and postural instability.

It is a chronic, progressive neurodegenerative disease caused by decreased production of dopamine, a neurotransmitter. Dopamine is responsible for most of the body’s smooth muscle movements. As a result, motor control in Parkinson’s patients is disrupted, causing anything from uncontrollable tremors to muscular stiffness to slow-as-molasses movements. (2) PD affects about 500,000 people in the United States, both men and women, with as many as 50,000 new cases each year. The disease usually begins in a person’s late 50’s and 60’s; it causes a progressive decline in movement control, affecting the ability to control initiation, speed, and the smoothness of motion. The symptoms of PD are seen in up to 15% of those between the ages of 65-74, and almost 30% of those were between the ages of 75-84. (3)Genetic RisksScientist identified two gene abnormalities present in PD patients whose families have a rate of the disease, indicating at least some evidence that the disease is inherited.

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Both abnormalities cause the body to produce an altered version of alpha synuclein, the protein that shows up in dense masses in the brains of Parkinson’s patients. (3). But in another study in the Journal of the American Medical Association suggested heredity is a significant influence on how fast the disease will onset. Researchers identified 172 twin pairs in which at least one twin had PD. If the condition was hereditary, the rate of both twins having the disease would be lower among fraternal twins, who share some, but not all of the same genes unlike identical twins who share them all. In individuals who were diagnosed after age 50, the rate of twins who both had the disease was similar among fraternal and identical twins.

In those diagnosed at 50 or younger, however, the rate was significantly lower in fraternal twins than in identical twins (2). Researchers also think that PD has environmental risks such as increase exposure to toxic chemicals such as pesticides, herbicides, or heavy metals. For example, some studies of people living in rural environments have shown a strong link with PD. In rural areas, well water is often not monitored properly and as a result, contamination from pesticides often go unnoticed. However, other studies show that this is not true, especially when rural toxins could only explain about 10% of Parkinson’s cases in the United States. (2)Symptoms and CausesThe immediate cause of PD is the degeneration of brain cell in the area known as the substantia nigra, one of the movement control center of the brain. Damage to this area leads to the cluster of symptoms known as parkinsonism.

In PD, degenerating brain cells contain Lewy bodies, which identify the disease. The cell damage that leads to parkinsonism may be caused by a number of conditions, including infection, trauma, and poisoning. When no cause of nigral cell degeneration can be found, the disorder is called idiopathic parkinsonism, or Parkinson’s disease. The substantia nigra, or black substance, is one of the principal movements control centers in the brain. The body releases a neurotransmitter known as dopamine; it helps to refine movement patterns throughout the body.

The dopamine released by nerve cells of the substantia nigra stimulates another brain region, the corpus striatum. If the brain does not have enough dopamine, the corpus straitum cannot control its target muscle control. As a result, the movement patterns of walking, writing, reaching for objects, and other basic programs cannot operate properly, and the symptoms of parkinsonism are the result. The symptoms of PD include tremors, which usually begin in the hand and on one side of the body and then the other. The classic tremor of PD is called a pill-rolling tremor, because movements resemble the pill rolling between the thumb and forefinger. Slow movements occur, which may involve slowing down or stopping in the middle of familiar tasks such as walking, shaving or eating. After a while the muscle rigidity or stiffness will occur with the jerky movements replacing smooth muscle. There are many other symptoms, a person experiencing these problems should immediately seek medical help.

(3) Parkinson’s Disease is a neuro-degenerative disorder that is widely assumed to be caused by oxidative stress or damage to the substantial nigra. The symptoms that most show are tremors, bradykinesia, and rigidity. There are also signs of some memory loss and cognitive functioning as well. There are several different proposed mechanisms of Parkinson’s but the most prevalent oxidative stress caused by free radicals, either genetic, environmental factors, and even just plain old chronological age. Another mechanism would have to be damage to dopamine or it’s turnover caused by the many forms of peroxidation. The brain needs the resources and time to battle the oxidative damage in order to keep the free radicals from harming the precious cerebullar granule cells, dopaminergic cells and neurons, and apoptotic cells to name a few. To make matters even worse, oxidative damage even affects genetic make-up of the bases of DNA.

There are other factors that also may play a role in the Parkinson’s disorder but they are not as conclusive. The true cause of Parkinson’s disease is not yet resolved and the disease is considered incurable and only gets worse as time goes on. It is the second most occurring neurodegenative disorder next to Alzheimer’s disease. A lot of the studies going on today are geared to the symptoms of Parkinson’s disease in its earlier stages. One of the most known lines of defense against oxidative stress would be antioxidants. Antioxidants are the leading preventive agent in the body to stop free radicals in their tracks.

In this review, the main focus will be on how the leading antioxidant in the body, Vitamin E (most commonly in the alpha-tocopherol form) fights off these free radicals and why it is one of the most important agents to fighting the early stages of this dreaded disease, Parkinson’s disease (1,5,9) Vitamin EVitamin E or alpha tocopherol is a major free radical chain-breaking antioxidant that plays a huge role in many studies that focus on the oxidative stress that is linked to the early stages of Parkinson’s. One of its main functions as an antioxidant is to fight lipid peroxidation and unsaturated lipids as well. Alpha tocopherol is found in the lipid bilayer of the cell membranes. It is in the human blood plasma and red blood cells (RBCs).

There it traps the free radicals by donating hydrogen to bound to the free radicals unpaired electron. Alpha tocopherol uses a technique to capture the radicals before they do further damage. The peroxide radical is transformed into hydro peroxide and the Vitamin E is left oxidized.

Vitamin C (ascorbate acid) then regenerates the Vitamin E to be able to function again. It is obvious that these two vitamins do work hand to hand to help prevent the oxidative damage. Vitamin C is essential because humans lack gulonolactone oxidase, an enzyme needed to convert glucose to ascorbate acid. Alpha tocopherol is also known to assist in the neutralization of free radicals in some cancers and reduce the risk of cataracts caused by oxidative damage to the lens of the eye. It is also shown to assist in the risks against coronary heart disease and hypertension (7). In the next few studies reviewed, researchers will illustrate how it is hypothesized that alpha tocopherol reduces the risk of many aspects of Parkinson’s (7,8,9). Vitamin E TherapyIn most cases, clinical studies have shown how alpha-tocopherol has some form of link to the symptoms of the Parkinson’s disorder.

According to Roghani and Behzadi, some clinical trials showed that Vitamin E therapy actually slowed down the progression of the disorder in people that had been diagnosed for a while. Also studies were done to see how vitamin E deficiency would affect the substantia nigral cells. This study will focus on the neuroprotective effect of Vitamin E in the early stages of Parkinson’s in rats. Vitamin E is thought to replace the enzymes that are needed to fight the radicals in the nigral neurons. It is also designed to look at the restraining dopaminergic cell damage in the rats and how they behave and function. There were labeled neurons on the rat to determine the effect that 6-hydroxydopamine-induced toxicity lesions, which causes a damage to certain brain cells, would affect the rat with the vitamin E. There were two groups: the pretreated rats with alpha-tocopherol and the lesioned ones.

The labeled neurons were 98% greater in pretreated than the lesioned ones. This is a good indicator that the neurons were spared in the event were oxidative stress to the cells could have occurred. The number of labeled neurons even months later and a higher level of Vitamin E helped stop the oxidative properties of 6-OHDA-induced toxicity. 6-OHDA toxicity causes damage to the nigrostriatal dopaminergic neurons that cannot be repaired. These free radicals are normally found in the neurons that can cause damage by superoxide dismutase (SOD), Glutathione peroxidase, and even a lighter form of glutathione.

Vitamin E regenerates the enzymes or mechanisms quickly against these radicals to ensure that the least amount of damage is done (8). Also Heim et al., supports this same toxicity is neutralized by alpha tocopherol. This study also supports the theory that Vitamin E does have positive effects in the very early stages of Parkinson’s disease (4). In the next study, it will focus more on how the deficiencies of the antioxidants, mainly alpha tocopherol and ascorbate acid, in the plasma can show signs or characteristics of neurological disorder, especially Parkinson’s. It has been shown by previous studies that there is an increased risk with the absence of antioxidants. The results of one study showed that the deficiencies did indeed prove to have certain mechanisms related to the oxidative stress by their absence.

It would be a reasonable assumption that low levels of the antioxidants may be toxic to the neurons because of the products of LDL-cholesterol oxidation. The reason for this would be that the free radicals are able to roam freely and cause significant damage to important neurological areas in the brain. More studies need to be done to truly conclude that without antioxidants like alpha tocopherol, Parkinson’s will be inevitable. This is why there are still some controversies about the causes of this disorder (7). Other studies have focused on the environmental factors, like herbicides, for some of the answers.

According to Gonzalez-Polo et al., Paraquat, an herbicide has a very similar structure to the dopaminergic neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) that produces Parkinson-like symptoms in humans, primates, and rats. Paraquat is a widely research herbicide to find out if there are any connections with radical oxygen species (ROS) when being used. Paraquat did cause death of some apoptotic cells and apoptosis is thought to play a role in neuronal cell loss in many neurological disorders, including our focus Parkinson’s. This study exposed rats to the paraquat to see if it caused any damage. Damage was recorded so researchers exposed another group and then injected them with the antioxidant alpha tocopherol. Alpha tocopherol provided the neuronal protection to the cerebellar granule cells by blocking all the early events observed in the infected rats.

The Vitamin E treatment blocked the cytochrome c release and cell death, proving that there is some connection between reactive oxygen species and cytochrome c translocation. This also suggests that the oxidative stress may be related to the xanthine oxidase system (1). Again, more research needs to be done to keep this convincing argument alive. This remains to be seen.

Conflicting ArgumentsSome have disagreed that Vitamin E does not have any affect on Parkinson’s disease symptoms. Nicoletti et al. suggest that this same notion.

Researchers do not denote that alpha tocopherol has antioxidant properties but the study showed no significant difference in the Vitamin E levels in Parkinson’s patients than in their control group. Researchers suggested that alpha tocopherol did not have any relation to the etiology of Parkinson’s disease but they still mentioned that the role of Vitamin E and its involvement with Parkinson’s is still not resolved and is controversial (5). Another clinical trial, found that deprenyl (selegiline) has some effects on Parkinson’s while alpha tocopherol was ineffective. Deprenyl given to lab rats slowed down the onset of Parkinson’s in the early, untreated stages were ineffective on the catecholaminergic neurons in the brain. According to this study, researchers reasonable assumed that the endogenous enhancer and psychostimulant with levodopa treatment made the alpha tocopherol treatment ineffective because of deprenyl’s enhancer effect. More research obviously needs to be done to find out whether or not this true (6). ConclusionIn conclusion, there is no doubt that Vitamin E (alpha tocopherol) the main chain breaking antioxidant is responsible for neuroprotection against free radicals. There is no way to pinpoint the exact reason for Parkinson’s though.

Parkinson’s disease is one of the most upcoming diseases in the elderly because people are living a lot longer. It is obvious that we do not have all the answers to this incurable disorder but we are making lead way. Oxidative stress is definitely one of the big players in the effects of many neurodegenerative disorders like Parkinson’s. The most important thing about these disorders is the education available to an individual to research. People should be informed about how these disorders came about in our everyday lives. Hopefully, more research will uncover some of the hidden aspects of this life changing disorder.

References1. Gonzalez-Polo, R.A., Rodriquez-Martin, A., Moran, J.M., Niso, M.

, Soler, G. &, J.M. (2004) Paraquat-induced apoptotic cell death in cerebellar granule cells. Brain Research 1011:170-176. 2. Health and Wellness Resource Center.

Ed. Christopher Saunders 2000 3. Health and Wellness Resource Center. Ed. Paula Ford Martin 2000 http://galnet. 4. Heim, C., Kolasiewicz, W.

, Kurz, T. & Sontag, K.H. (2001) Behavioral alterations after unilateral 6-hydroxydopamine lesions of the striatum effect of alpha-tocopherol. Pol. J. Pharmacol.

53:435-448.6.Nicoletti, G., Crescibene, L., Scornaienchi, M.

, Bastone, L., Bagala, A., Napoli, I.D., Caracciolo, M. & Quattnone, A. (2001) Plasma levels of Vitamin E in Parkinson’s disease.

Archives of Gerontology and Geriatrics 33:7-12. 6. Miklya, I., Knoll, B.

; Knoll, J. (2003) A pharmacological analysis elucidating why, in contrast to (-)- deprenyl (selegiline), alpha-tocopherol was ineffective in the DATATOP Study. Life Sciences 72:2641-264810.

Parashevas, G.P., Kapaki, E.

, Petropoulou, O., Anagnostouli, M., Vagenas, V. ; Papageorgiou, L. (2003) Plasma levels of Antioxidant Vitamins C and E are decreased in vascular Parkinsonism. Journal or Neurological Sciences. 215:51-55.

11.Roghani, M. ; Behzadi, G., (2001) Neuroprotective effect of vitamin E on the early model of Parkinson’s disease in rat: behavioral and histochemical evidence. Brain Research 892:211-217. 12.

Vatassery, G.T., Demaster, E.G., Lai, James C.

K., Smith, W.E. & Quach, H.T. (2003) Iron uncouples oxidative phosphorylation in brain mitochondria isolated from vitamin E-deficient rats.

Biochemical et Biophysical Acta 1688:265-273..