Diseases of the brain are some of the most complex and difficult to treat conditions. One such disease is Parkinson’s disorder, which is thought to be caused by the death of neurons that produce dopamine, a neurotransmitter that has been called the “pleasure chemical” but is also involved in making movement possible. The decrease in dopamine can lead to symptoms such as tremors in the extremities and loss of balance, which can increase the risk of falling. Unfortunately, the specific mechanism behind how these dopamine neurons die is not currently known. Although the disease is primarily associated with the elderly, it has also been diagnosed in relatively younger individuals around the ages of 21-50. These earlier cases are called young-onset Parkinson’s disease (YOPD) and arguably gained wide recognition following actor Michael J. Fox’s diagnosis of YOPD at the age of 29. Significant research efforts have gone towards uncovering the mysteries of Parkinson’s, and a recent study may help lead us closer towards the ultimate goal of finding a cure.
Image Source: Sherbrooke Connectivity Imaging Lab (SCIL)
Researchers from Cedars-Sinai found that dopamine-producing neuronal cells derived from patients with YOPD had elevated levels of alpha-synuclein, one of the first proteins to be associated with Parkinson’s, and reduced levels of lysosomal membrane proteins, which results in the impairment of lysosome function. Lysosomes are organelles involved in the degradation of macromolecules (carbohydrates, lipids, proteins, and nucleic acids). Due to the invasive technique required in order to extract neuronal cells from these YOPD patients, the researchers instead took blood cells, reverted them into induced pluripotent stem cells, and then caused those cells to turn into the neuronal cells of interest. The inability of lysosomes to properly execute their degradation function may explain the excessive amounts of alpha-synuclein in the dopamine neurons. To test this hypothesis, drugs like PEP005, which help activate lysosomes, were introduced to these neuronal cells in both in vitro and in vivo experiments; they found alpha-synuclein levels to be reduced in both cases following drug treatment. Interestingly, PEP005 is already an FDA-approved drug that is currently being used to treat leukemia.
Image Source: UCSF
These results suggest that early diagnosis of YOPD and early treatment may help prevent the progression and worsening of Parkinson’s disease. Although it is still unclear as to how exactly alpha-synuclein causes different forms of Parkinson’s, it is reassuring that there is now a potential new method to reduce the levels of this protein in addition to those described previously. However, it is certain that much more research needs to be done in terms of understanding how Parkinson’s disease occurs before a cure can be discovered.
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