Toxic Proteins That Cause Parkinson’s Disease Could Originate in the Gut

A gut brain connection has been established in recent studies but the mechanism of the connection has not been fully detailed. Scientists have provided little evidence about the possible ingestion of toxins or germs which could lead to damage to the brain and the subsequent symptoms of Parkinson’s disease. A research team from the Duke University has discovered insights into how endocrine cells increase in numbers in the small intestine. The protein, alpha-synuclein, present in these cells are known to result in clumps in the brain that results in Parkinson’s disease

Gut-Alpha-synuclein Connection

The study was published in the journal JCI Insight, in which the research team from Duke University, along with collaborators from the University of California, San Francisco, has detailed how agents present in the gut, may play an important role in the concentration of alpha-synuclein, resulting in the deformation of the protein. The alpha synuclein protein that are deformed would then spread to the brain via the nervous system, using a mechanism similar to that of the mad cow disease, and like an infectious protein.

Dr. Rodger Liddle, who is the senior author of the study, said that there was abundant evidence obtained about the presence of deformed alpha-synuclein present in the gut even before it is identified in the brain, though the mechanism behind the misfolding was unknown. The gastroenterologist said that this study provided conclusive evidence that Parkinson’s disease developed in the gut rather than the brain.

Alpha-synuclein has been in the center of a lot of research as it is one of the important components of lewy bodies, which are the protein deposits that are present in the brain cells of Parkinson’s disease patients, killing the brain cells from inside. Alpha-synuclein has a spiral structure which is disrupted and becomes sticky, leading to aggregation.

Entry Into the Nervous System

The major hurdle that the research team from Duke University had to overcome was to identify how the misded protein traveled past the intestine, where there are no nerve cells, into the central nervous system. The research team sought to answer this in their study published in the Journal of Clinical Investigation (2015), which detailed how the endocrine glands in the gut, which are primarily associated with digestion, also have nerve like properties.

These endocrine glands present in the gut communicate with the nervous system by physically connecting with the nerve cells, instead of communicating indirectly using hormones. This provides a channel of communication, which was demonstrated by a time lapse video put together by the research team. The endocrine cells moved towards the neurons within a span of a few hours and established connection with them, which was demonstrated by the development of fibers between them.

Transformation of the Endocrine Cells

The most startling aspect of the video developed by Liddle and colleagues was that the endocrine cells began to behave like nerve cells, even though they were not nerve cells. This showed that the endocrine cells could establish a direct communication mechanism with the nervous system and the brain. This insight into the mechanism of movement of the misfolded alpha synuclein into the brain was possible due to the discovery of alpha-synuclein in endocrine cells.

Identifying a Biomarker

The next step in this research being conducted by Dr. Liddle and his research team is to isolate the gut endocrine cells from Parkinson’s disease patients and to identify if the misfolded alpha-nuclein protein is present in these cells. This will help in determining if alpha- synuclein is a potential biomarker for the development of Parkinson’s disease.

The misfolded protein could also be used as a target for future therapy for Parkinson’s disease, though there are already research studies that are associated with preventing the folding of alpha synuclein they are only in the initial stages of study, there is currently no effective treatment measures for Parkinson’s disease.

Parkinson’s Disease

Parkinson’s disease is a disorder of the central nervous system which leads to a progressive movement disability. The disease primarily affects the substantia nigra present in the nervous system and current treatment measures are focused on delaying the progression of the disease.

An understanding of the mechanism of development of this disease will help in developing therapeutic strategies that prevent the progression of the disease and could improve symptoms associated with the condition. There are more than 1 million people in the U.S and nearly 7 lakhs in India with this condition, however, lack of effective treatment affects the quality of life lead by these patients. Identifying the biomarker for the condition will help in developing therapeutic strategies to prevent this condition.

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Reference:

1. What is Parkinson’s Disease? - (http://www.pdf.org/about_pd)
2. Research in Parkinson's disease in India: A review - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782561/)

Source-Medindia