Neurodegenerative Diseases: Including Therapeutic Advances and An Excess of Biological Background (sorry)

The neuropsychological topic that I chose to investigate was neurodegenerative diseases.  Because of the heavily medical and biological nature of this subject I did a little bit of basic background research in order to better understand the nature of the diseases and the primary research papers.

Firstly, neurodegeneration is the progressive loss of structure and function of neurons including the death of neurons.  Common neurodegenerative diseases include Parkinson’s, Alzheimer’s and Huntington’s.  On a very biological level, many neurodegenerative diseases are caused by genetic mutations, specifically the repeat of a CAG nucleotide triplet.  This nucleotide triplet encodes for the amino acid glutamine, thus diseases caused by this genetic mutation are known as polyglutamine diseases.  There are nine inherited neurodegenerative polyglutamine diseases including Huntington’s.  Similarly, Parkinson’s is caused by abnormal aggregates of proteins as well; these aggregates are known as Lewy bodies and develop inside nerve cells.  Diseases caused by the accumulation of intracellular toxic proteins that lead to the eventual degeneration of neurons are categorized as proteinopathies.  Many other neurodegenerative diseases are caused by neuron death.  The most common form of cell death in neurodegeneration is through mitochondrial dysfunction resulting in apoptosis.  Reactive oxygen species (ROS) are normal byproducts of mitochondrial activity but when there is mitochondrial dysfunction over production of ROS occurs resulting in oxidative stress, a central feature of all neurodegenerative disorders.  Thus it is very likely that mitochondrial dysfunction and oxidative stress play a largely causal role in neurodegenerative diseases.  Lin and Beal (2006) conducted research on the relationship between ROS and neurodegeneration.  Finally, the greatest risk factor for neurodegenerative diseases is aging.  Many neurodegenerative diseases are late-onset which indicates there is some factor that changes with aging; in each disease neurons gradually lose function as the disease progresses with age.

On a medical level, protein degradation treatments are being studied heavily; recent research by Rubinsztein (2006) studies the roles of intracellular protein-degradation pathways in neurodegeneration.  The treatments involve helping to prevent the synthesis of irregular proteins and the process which leads to eventual degradation of neurons but involve very complex pathways that are only beginning to be understood.  There is also research by Brody and Holtzman (2008) involving immunotherapy in order to enhance the innate immune system against Alzheimer’s.

As far as research on treatments for Parkinson’s, there is extensive research on transplantation of embryonic stem cells to encourage neurogenesis, or growth of new neurons.  W.C. Low (1982) showed that transplantation of embryonic dopamine neurons into the brains of animals with animal model Parkinson’s has been shown to improve many of the impaired motor functions.  Lindvall and associates (1989) provide moderate evidence in support of embryonic dopamine implants improving human Parkinson’s patients motor functioning.

There is much work that has been done but also much work to be done in the study of neurodegenerative diseases.  As research progresses, many similarities appear relating these diseases to each other on a sub-cellular level.  These similarities offer hope for therapeutic advances in not just one, but many neurodegenerative diseases simultaneously.

9 thoughts on “Neurodegenerative Diseases: Including Therapeutic Advances and An Excess of Biological Background (sorry)

  1. wow. there really is an excessive biological background to neurodegenerative diseases. As I sit back and ponder about these incredibly devastating diseases in which your againg brain is deteriorating at the height of experience and wisdom as a human being, I am curious as to why these diseases exist in nature? Is it simply a case of survival of the fitest or is it the brain’s way of protecting the aging sufferers from the preoccupation of death and the end of life?


  2. While reviewing erikson’s Psychosocial stages, I saw that the dichotomy in old age is integrity vs. despair. In this final stage of life, individuals reflect on the kind of person they have been. Integrity results from feeling that life was worth living as it happened. Old people who are dissatisfied with their lives fear death.

    I wonder how a neurodegenerative effects these particular dichotomy. Could it prevent older individuals from gaining closure in life?


  3. Neuodegenerative Diseases are near and dear to my heart. I really hope I can study some of these diseases in extreme detail one of these days. In terms of the biology, there is a ton of research on the different ways stem cells can help alleviate some of the symptoms caused by neurodegeneration. Perhaps the effects are not long lasting… I am really enjoying this new area of research on induced pluripotent stem cells (IPSCs), which allows scientists to take our somatic cells and make them pluripotent. Basically, they can differentiate into any of the three germ layers. You can even grow these stem cells in vitro and then transplant them into the brain. With respect to the formation of teratomas, I think cellular therapy can help some of the biological and psychological problems we see neurodgenerative diseases.


  4. I wonder if the fact that we do undergo neurodegeneration is a sign that we aren’t supposed to live so long. Are we living unfulfilling, artificial lives? I know this is sad but were individuals more happy when they died at earlier ages. Lia’s comment that neurodegeneration makes the later stages of life less fearful made me think that they aren’t a coping mechanism. Humans may just be outliving their brain’s life. With the prolonging of human’s lifespans we need to also consider prolonging the endurance of our other organs


  5. That really makes me wonder, too, if neurogeneration is nature’s way of telling us to try to stop being so smart! Or, that if we’re going to be smart alecks and try to defy nature by keeping people alive so long, we’d better step our game up and be that smart all-around (as in, figure out how to better prompt neurogeneration. I didn’t realize that proteins were an active agent in neurodegeneration- I just assumed it was a the neurons themselves dysfunctioning, not being the victim of something else. Interesting!


  6. Just to play devil’s advocate- if it was the case that neurodegeneration is nature’s way of telling us that we aren’t supposed to be living this long/ or to stop being too smart, why does it only seriously occur in some aged brains and not others? For instance, an aunt of mine is suffering from severe Alzheimer’s Disease while her sister (two years older) is as fit as a fiddle. How does this selectively occur to some and not others. Evolutionary speaking, and keeping in line with what you guys said, it seems like you have a possible Darwinian way of reasoning this where it all boils down to survival of the fittest? I have never really thought of it in that way before! Definitely novel and interesting to me!


  7. I think that it is very interesting that there are so many ways in which we can possibly treat these diseases–especially in the age of stem cell research. What frustrates me, however, is the reluctance of people to allow this research to progress. While I won’t get into the moral arguments surrounding this debate, I will say that I think it is more immoral to deny someone suffering the opportunity to be better based on the ‘possibility’ that we’ve “destroyed a life” by using stem cells. Just a thought. I feel like the established life is of more importance, but who am I to judge.

    Also, I agree with Darshini, even thought she is playing devil’s advocate. This really does seem quite darwinian. Think about it-every other species will thrive if given the space and resources-but the environment is limited. We have just figured out how to cheat mother nature and go against simple evolution with our technology. This can be said for many other things, but again I won’t go into it 🙂


  8. In terms of stem cells, I definitely believe that it is a moral issue. I think people should believe what they believe. On the other hand, people are really excited and invested in the IPSCs. We completely bypass the debate by turning fat cells/skin cells into stem cells. There is even an added bonus! By using personal cells people don’t have to keep taking immunosupressants.

    Good point Darshini. Perhaps the good genes always win.


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