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The Neurobiology of Parkinsons Disease, part 2: further research and parallels to Alzheimers?

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The Neurobiology of Parkinsons Disease, part 2:
further research and parallels to Alzheimers?

Rani Shankar

In my previous paper, the basic pathogenesis and neurobiology of Parkinsons Disease was discussed. Parkinsons Disease is recognized as a progressive neurodegenerative condition that is believed to be caused by a combination of genetic and environmental factors. Parkinsons Disease is characterized by a deficit in dopamine, a neurotransmitter produced in the substantia nigra, that is responsible for maintaining normal motor functioning. This paper will continue the exploration of Parkinsons Disease research, also examining Lewy Bodies, genetic factors, and drawing parallels and possible links to Alzheimers Disease.

Lewy Bodies, aggregated eosiphilic cytoplasmic inclusion bodies found in substantia nigra, are a hallmark characteristic of Parkinsons disease identified by pathological studies. As mentioned in my previous paper, Lewy Bodies are not able to be used to diagnose Parkinsons, as they are only observable during an autopsy, but are a fool-proof method of identifying the disease, after the fact. Lewy Bodies are present in dementia and found in some cases of Alzheimers Disease. In Parkinsons, the cells of the substantia nigra die, so that the normal dark brown pigment (hence, the name, nigra) is instead pale. The Lewy Bodies are among the dying nerve cells left in the substantia nigra (1). Lewy Bodies provide a connection to both Alzheimers and dementia hinting that there might be a common mechanism underlying these diseases. Since these conditions have a broad range of neurological symptoms, this has significant implications in their connections between motor control and cognition.

In Parkinsons Disease, as in associated neurological conditions like Alzheimer's, Lewy Body Dementia, and Schizophrenia,we observe a correlation between the brain and behavior. The Parkinsons Disease example illustrates many of the fundamentals of neurobiology, whereby uncovering the process of neurodegeneration and malfunction, we can better understand the inner workings and functionability of the nervous system. The general symptoms of Parkinsons Disease include tremors of the body (even at rest), stiff limbs, slow movements, lack of facial expression, shuffling gait, and a stoop. It is sometimes accompanied by such symptoms as depression, impaired cognition. All the above presentations of the disease result from neuronal degeneration. Thus, the diverse neurological symptoms of Parkinsons Disease illustrate integrated functioning of the nervous system and further proving the intimate interconnectedness of the brain and behavior. The integrated-ness of the study of Parkinsons Disease allow many entres to research. Some scientists approach the study of the disease via the brain; by illuminating the anatomy of the command centers of brain, the function of the motor system and how it regulates movement can be better comprehended (2). Drug therapies are being developed to alleviate Parkinsons symptoms and possibly prevent, or reverse disease progression (2). Environmental factors have continued to be studied to measure the effects of toxin build-ups on the growth of nerve cells. Additionally, the genetic component of the disease has been examined to demonstrate that certain groups have a susceptibility to developing the disease (2).

Interest in the genetics of Parkinsons Disease has recently escalated with the identification of a Parkinsons gene. Nussbaum and Polymeropoulos, published in the Nov 15, 1996 issue of Science, proposed that Parkinsons Disease is an autosomal dominant disorder. They observed a genetic linkage and a common idiopathic form of Parkinsons passed through families (3). These pathological symptoms included the presence of Lewy Bodies distributed evenly throughout the substantia nigra, hypothalamus, hippocampus, autonomic ganglia, and olfactory tracts (3). The gene was identified on chromosome 4, 4q21-23, alpha-synuclein, which encodes a presynaptic protein whose mutant form is known to cause plaques in Alzheimers Disease (3). It is thought that in families with a history of Parkinsons Disease there is a missense mutation in the alpha-synuclein gene which prevents normal protein degradation, eventually leading to nerve cell death.

These results are significant in that it approaches the cause of Parkinsons from a whole new perspective. Before it was thought that Parkinsons stemmed from entirely environmental factors. Previous studies identified Parkinsonian symptoms in MPTP (meperidine) drug users, demonstrating the neurotoxicity of MPTP build-up (4). MPTP is speculated to inhibit mitochondrial DNA function, and through a number of cellular pathways breaks down dopamine. Parkinsons Disease is thought to function similarly. Using MPTP studies, scientists developed the drug seligiline, which allows for normal storage of dopamine and delays the presentation of Parkinsonian symptoms. It is likely that environmental factors, which may include the build-up of toxins such as MPTP, combined with genetics, contribute to the development of Parkinsons Disease. Although further studies are needed to substantiate this data, this evidence has a significant impact on the directions of future research.

Scientists are also exploring the possibilities of neural grafting in order to rejuvenate degenerated neural cells. Studies out of NINDS have demonstrated that animal models with implanted fetal tissue from the substantia nigra into a brain with Parkinsons, causes damaged cells to regenerate. The regenerated dopamine-producing cells are able to improve motor skills and increase response to medications (2). The philosophical and ethical implications prompted by this study are infinite. Although the benefits of such a practice a numerous, how does the implantation of fetal tissue into the brain affect or influence notions of the I-function? How do we reconcile the development of fetal cells for such a study? More recent studies suggest that it may be possible to use modified skin cells, genetically engineered, that could operate similarly to replenish normal neuronal activity (2). This would eliminate controversy over donors and therefore, the cells would be easier to cultivate (2).

When considering much of the research done thus far on Parkinsons Disease, many findings parallel those of Alzheimers Disease. Alzheimers is also a neurodegenerative condition associated with aging. Both Parkinsons and Alzheimers Disease are thought to result from a combination of environmental and genetic factors and are thought to respond to common drug therapies, namely L-dopa (5). Alzheimers Disease progression is more internal, as opposed to the deterioration of motor movement in Parkinsons, and is characterized by a gradual loss of short-term memory . Memory dysfunction is also accompanied by changes in personality and mood. Although their disease symptomizations are distinct enough, their mechanistic similarities are nothing to sneeze at. Interestingly though, both conditions carry symptoms of dementia. Recently there have been cases of simultaneous Parkinsons and Alzheimers symptoms (5). Both diseases are now characterized by the presence of Lewy Bodies, as recent autopsy studies at the University of Pittsburgh Alzheimers Disease Research Center have shown that there are also found in Alzheimers. Though, where Parkinsons Lewy Bodies are confined to the base of the brain, Alzheimers Lewy Bodies are found diffuse throughout the whole brain (5). As mentioned above, the gene associated with familial Parkinsons, alpha-synuclein, is also connected to Alzheimers symptoms. When there is a mutant form of the gene, as in Parkinsons, it is known to cause plaques identical to those of the Alzheimers example. Thus, the overlap in symptoms, treatments, and underlying mechanisms in both of these diseases suggest that similar anatomical changes are displaying, for the most part, diverse symptoms.

In conclusion, Parkinsons Disease research can be advanced by further exploring links and overlaps with other neurodegenerative disorders, such as Alzheimers. By comparing the epidemiology of these conditions, it is realized that huge impact of the functioning of the brain and behavior. With recent evidence of a definite genetic component and success in neuro-transplantation research, the damage done to nervous system as a result of Parkinsons may not as permanent as previously thought.

References

1. Dementia with Lewy Bodies. LEWYNET from Nottingham Med School.

2. Research Studies on Parkinsons Disease. Health Touch.

3. Genetics of Parkinsons Disease. Human Molecular Genetics Abstract. Pub Med.

4. Parkinsons Disease. OMIM. Online Mendelian Inheritance in Man.

5. Alzheimers and Parkinsons: A link? University Times. University of Pittsburgh.

 

Comments made prior to 2007

My husband 60 has Parkinson's and his sister 63 has beene diagnosed with Alzheimers. Her condition is such that she is no longer able to work and my husband is still working for a while.

We are doing much reading and are scheduled to be seen by clinic in Springfield, Il (SIU School of Medicine) for testing. Belief is that this is not only familial but that these diseases overlap as stated. They
both have Parkinsonisms that we think are directly related to the fact that the praternal side of the family shows 4 others who have/had both of these diseases.

Hoping to help these two as well as offer some information realtive to the other 3 siblings and the children and grandchildren.

We have to always ocntinue to explore and be an advocate for those who are not able..much information out there and be assertive with your journey for diagnosis, treatment and clinical trials for helping the generations to come ... Sue Knight, 12 February 2006

 

 

My father was diagnosed with Parkinsons when he was 52. He died in 2001 at 72. He lived for quite a while in Central Wisconsin (Plover). Was told not to drink the water because of pesticide run-off. But he showered in it daily. Now his wife, my stepmother, who is 74 has been diagnosed with Parkinson's. How much do we know about pesticides and their affects on people. And has there been a study to see how many people in this farming community have Parkinsons? Thanks for your time ... Norma Hilliard, 23 August 2007

Comments

Paul Figthing Parkinson's's picture

Figthing Parkinson's

It was great a research about Parkinson's I also want to add extra information about parkinson's. Parkinson's disease (PD) is a degenerative disorder of the central nervous system that affects neurons that control movement, leading to impairments in the sufferer's motor skills, speech, and other functions. Parkinson's belongs to a group of neurologic conditions called motor system disorders, which are the consequence of the insufficient formation and action of dopamine by dopaminergic neurons in the substantia nigra of the brain. Dopamine normally transmits signals that help coordinate movements. The mechanism that results to the damages of these cells remains unknown. As Parkinson’s progresses, patients may present with difficulty walking, talking, or accomplishing simple tasks. The disease usually affects people over the age of 50 and it is more common in men than women. The early symptoms are subtle and develop slowly, but in some patients the disease can progress more quickly. Thank you for sharing. very helpful. Paul

naveen  's picture

cases

I need cases of Parkinsons diseases.
Pls help.

Paxil side effects's picture

Slightly confused here

Is there some connectivity between Alzheimers & Parkinsons disease?Please let me know...i am a bit confused.

SJS's picture

A great deal of information

Alzheimers Disease just sounds to be so dangerous, loosing memory to an extent that you are not even in condition to recognize your own people,just thinking about it gives me goose bumps.I must say that you have provided a great deal of information on the topic.Thanks for sharing.