There is currently no cure for Parkinson’s disease (PM), and one of the main difficulties in developing treatments is that we don’t know exactly how or why the disease occurs. An accumulation of Lewy bodies, cell inclusions that contain mainly brain-specific alpha-synuclein protein, is generally thought to cause cell death in key regions of the brain, leading to typical symptoms of MP. . However, a recent report published in Movement Disorders by researchers at Osaka University suggests that this is not the only way PD-related cell death can occur.
The report describes a patient who had what appeared to be a standard MP, with no family history or disease-related genetic mutations. He had typical DP motor symptoms such as stiffness, slow movement, and balance problems. He also had reduced dopamine (which helps cells talk to each other) in a region of the brain known as a striatum and responded well to treatment with a drug called levodopa, which is commonly seen in people with PD.
After the patient died of pneumonia, his brain was examined closely. Although it had many of the common changes seen in PD (such as a loss of brain cells and an increase in inflammation in the substantia nigra, a key brain region related to PD), some other typical changes were missing. . The researchers were unable to find Lewy bodies containing alpha-synuclein in any of the regions that are normally affected by PD.
This was unusual. When we looked further, we realized that the patient had inclusions that contained another type of protein: the 43 kDa transactive response DNA binding protein or TDP-43 ”.
Rika Yamashita, lead author of the study
TDP-43 protein accumulation occurs in other neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration, but is not normally associated with MP. However, this new report suggests that its accumulation may lead to cell loss in the substantia nigra, as well as the typical motor symptoms of MP.
“This report has implications for how we think about the development of DP,” explains Goichi Beck, lead author of the report. “Much of the current research looking for treatments for MP is very focused on alpha-synuclein, but it may not be the only protein that causes the disease. Our results indicate that TDP-accumulation 43 may be a cause of MP separated from alpha-synuclein. Accumulation. “
Future studies should consider TDP-43 when investigating the mechanisms that cause PD in the brain. The findings of this research suggest a new pathway to develop MP and may lead to the discovery of new treatments that slow down or cure the disease, which are currently lacking.
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Magazine reference:
Yamashita, R., et al. (2022) Presentation of TDP-43 proteinopathy with typical symptoms of Parkinson’s disease. Movement disorders. doi.org/10.1002/mds.29048.