Revolutionizing Parkinson's Disease Treatment: The Role of Propionate

Category Health

Saturday - March 30 2024, 16:54 UTC - 1 year ago

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A recent study led by Professor Zheng from HKU has found that propionate, a short-chain fatty acid produced in the gut, can suppress neurodegeneration in animal models of Parkinson's disease (PD). Through its role in interorgan signaling between the intestine and brain, propionate promotes energy production and neuronal health, providing a potential new strategy for treating PD and other neurodegenerative diseases.

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Parkinson's disease (PD) and Alzheimer's disease (AD) are two of the most common neurodegenerative diseases, affecting millions of people worldwide. Despite extensive research, traditional treatment methods that target protein aggregates in the brain have had limited success in slowing or reversing the progression of these diseases. However, a recent study led by Professor Chaogu Zheng from the School of Biological Sciences at The University of Hong Kong (HKU) has revealed a new perspective on treating PD by targeting the gut microbiota and its metabolites.

PD and AD have traditionally been treated by targeting protein aggregates in the brain, however this has limited success.

The study, published in the journal Cell Reports, focuses on the role of a specific short-chain fatty acid (SCFA) called propionate in suppressing neurodegeneration in animal models of PD. SCFAs are produced in the gut through the fermentation of dietary fiber by anaerobic bacteria. They have been a topic of interest in recent years due to their potential impact on various bodily functions, including brain health.

Recent studies suggest that gut microbiota and their metabolites play a crucial role in neurodegenerative diseases.

Previous studies have shown conflicting findings on the effects of SCFAs on neurodegeneration. While some suggest that SCFAs worsen neurodegenerative diseases, others have found evidence that they may have protective effects. To further investigate this, Professor Zheng's team used a C. elegans PD model and identified 38 pro-neurodegenerative genes in E. coli. Interestingly, some of these genes are responsible for the production of vitamin B12, which induces the breakdown of propionate in the host.

Short-chain fatty acids (SCFAs) are produced in the gut by anaerobic bacteria from dietary fiber.

The team's hypothesis was that increasing the levels of propionate may suppress neurodegeneration. Through their study, they found that PD animals had significantly lower levels of propionate compared to normal animals. Increasing propionate levels either by removing dietary vitamin B12 or through direct supplementation rescued alpha-synuclein-induced neuronal death and locomotion defects in the PD models.

Controversial findings on the effects of SCFAs on neurodegeneration have hindered further research.

What surprised the team was that the neuroprotective effects of propionate were not solely due to its functions as a SCFA but rather its interorgan signaling between the neurons and the intestine. In PD models with alpha-synuclein aggregation, there is an increase in mitochondrial unfolded protein response (mitoUFR), which suppresses the transcription of an enzyme responsible for propionate breakdown. As a result, there is an accumulation of propionate inside the intestine. This increased concentration of propionate in the intestine promotes energy production and stimulates the expression of mitochondrial chaperonins, ultimately leading to the survival of neurons.

The team from HKU previously identified 38 pro-neurodegenerative genes in E. coli using a C. elegans PD model.

These findings provide important new insights into the treatment of neurodegenerative diseases, suggesting that increasing propionate levels may be a potential therapeutic strategy for PD and other related diseases. Further research is needed to fully understand the mechanisms involved and to explore the potential use of propionate as a treatment for these debilitating diseases.