One of the significant hurdles in finding the treatment of any of the neurodegenerative diseases is the limited knowledge regarding the underlying mechanism. It is known that Parkinson’s and many other neurodegenerative disorders occur due to the buildup of malformed proteins. In the case of Parkinson’s, the death of dopamine-producing cells in the substantia nigra and accumulation of Lewy bodies are just two of the hallmarks of the disease.
What is known is that there is some relationship between the disease's onset and genetics, however, it seems that the importance of environmental factors is also tremendous. There have been many mechanisms proposed about how the combination of genetics and environmental triggers that may lead to progressive cell death in certain parts of the brain that lead to the development of Parkinson’s.
Recent research seems to indicate that various factors lead to mitochondrial and lysosomal dysfunction, leading to progressive cell death in Parkinson’s.
Mitochondria are the energy houses of body cells, and their dysfunction may lead to cellular damage, malfunctioning, or even death. Lysosomes are small vessels that contain various enzymes needed for cellular digestion, and they also have a role to play in the cell death and clearance of debris. The latest research seems to indicate that the alterations in mitochondrial and lysosomal functioning may have a central role in brain cells destruction involved in Parkinson’s.
During the last few decades, researchers have been trying to decode the cascade of events causing neuronal death in Parkinson’s, in order to find out the ways of interrupting this cascade and thus preventing the disease's progression, or even by reversing the disorder.
Scientists at Northwestern medicine have found a new toxic pathway, a toxic cascade that may be central to how Parkinson’s disease progresses. They also demonstrated the effectiveness of specific interventions in interrupting the cascade, thus raising the hopes of finding a way to prevent the disease's progress in early stages.
Burbulla et al., at Northwestern University Feinberg School of Medicine, published a study in the journal Science, in which they demonstrated the beneficial effects of specific antioxidants in preventing disease progression in Parkinson’s, if the therapy is initiated early enough.
Parkinson’s is one of the most common disorders of the brain that causes movement disorders. Though it may not be acutely fatal, it is highly incapacitating. It is a disease that is caused by a deficit of dopamine in specific neural pathways because of the death of neurons at particular locations in the brain. More precisely, due to the destruction of neurons at substantia nigra. The substantia nigra is as mall region of the brain that plays a vital role in both the motor function and reward pathway or the limbic system.
Although the progressive loss of brain cells is normal in aging, with Parkinson’s, this loss of neurons is so significant in specific brain areas that our brain is no longer able to compensate for such losses, thus resulting in the slowness of movements, tremors, and difficulties of movements.
There have been lots of studies that indicated the mitochondria and lysosomes are two micro organelles in the neurons playing a role in the death of brain cells. Nonetheless, researchers have failed to explain the reason of malfunctioning of these small cellular structures until now. So, understanding the mechanism of cellular degeneration is considered to be a significant step forward.
So, what did the researchers exactly do to confirm the mechanism of cell death in Parkinson’s?
Burbulla and their colleagues used the brain cells from the patients that were known to be suffering from Parkinson’s to pinpoint the mechanism of cell death, chemical reactions or cascades that were involved in the disease progression. They found out that everything started due to the buildup of a faulty neurotransmitter called oxidized dopamine.
Burbulla and team said that if one can find a way to diagnose Parkinson’s at the very early stage, it is entirely possible to break this toxic chain reaction with the help of specific antioxidants.
What researchers noticed is that the buildup of oxidized dopamine resulted in the malfunctioning of lysosomes, these lysosomes, in turn, damaged the cellular mitochondria. This results in a further increase in accumulation of oxidized dopamine. So, the buildup of oxidized dopamine initiated the chain reaction that resulted in continued damage to cells. Researchers noticed the build-up of a vicious circle.
Once they realized how this cascade works, they began to search for the ways to interrupt this reaction, to break the vicious circle. They found that some specific antioxidants were effective in doing so, though they only worked when used at the very early stages.
Burbulla and team concluded that any treatment approach that is effective in modifying the course of Parkinson’s by use of antioxidants requires that they must be used in the early stages of the disease. Their finding opens an area for future research; it provides the hope that one day we would be able to disrupt this cascade in its infancy and prevent the disease's progress.
Unfortunately, at present, there is no method available to detect Parkinson’s in its primary stages. Although, it is well-known that, quite like other neurodegenerative diseases, Parkinson’s starts years or even decades before the first symptoms appear.
Various diagnostic methods are providing hope for an early diagnosis of Parkinson’s with high accuracy. It is already known that specific genes and genetic mutations are related to the development of Parkinson’s in the later life. Moreover, scientists have identified many other factors that could help predict the risk of Parkinson’s disease.
Apart from genetic testing, it is quite probable that in the future detection of particular biomarkers in the blood, or results of brain imaging may also be able to predict the risk of Parkinson’s, and even other neurodegenerative diseases.
Researchers are also learning to identify signs or health changes that could forecast the risk of neurodegenerative diseases, like alterations in personality, modifications in the sleep pattern.
At present, there is no foolproof method of predicting the risk of Parkinson’s in later life. Nonetheless, there is hope that things would change for the better in coming times. And there is hope that some therapeutic drugs would be substantially able to reduce the risk of neurodegeneration, thus helping to prevent the prevalence of Parkinson’s and other similar diseases.
- Burbulla LF, Song P, Mazzulli JR, et al. Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease. Science. September 2017:eaam9080. doi:10.1126/science.aam9080
- Power JHT, Barnes OL, Chegini F. Lewy Bodies and the Mechanisms of Neuronal Cell Death in Parkinson’s Disease and Dementia with Lewy Bodies. Brain Pathol. 2017;27(1):3-12. doi:10.1111/bpa.12344
- Wakabayashi K, Takahashi H. [The mechanism of Lewy body formation in Parkinson’s disease]. Nippon Rinsho. 2000;58(10):2022-2027.