The most visible symptoms of Parkinson's disease, the tremors and loss of motor control, result from the death of a small but vital population of dopamine-generating neurons in the brain. These neurons happen to be more sensitive than others to the underlying harmful biochemistry of the condition. Parkinson's disease begins with the misfolding of α-synuclein, one of the few proteins in the body that can become altered in a way that encourages other molecules of the same protein to alter in the same way, joining together to form solid aggregates. These α-synuclein aggregates are disruptive to cell function and ultimately toxic, causing cell death.
In recent years it has become clear that a sizable fraction of Parkinson's disease begins in the intestines. The initial α-synuclein misfolding occurs there, and then slowly spreads through the nervous system to the brain. In today's open access paper, researchers provide evidence for a specific bacterial species found in the gut to be responsible for producing this initial misfolded α-synuclein. It remains to be seen as to whether further human gut microbiome studies will replicate the results here and further support a role for bacteria in the origination of Parkinson's disease, or whether it is only a smaller fraction of the overall incidence of Parkinson's disease that has a bacterial origin.
To the extent that bacteria are capable of producing a sizable amount of misfolded α-synuclein in comparison to natural misfolding in human cells, one might expect to find it responsible for a majority of the incidence of Parkinson's disease. While this discovery may lead to the prevention of much of Parkinson's disease in the best case scenario, it doesn't much help those people who already have misfolded α-synuclein present in the central nervous system; at that point it is too late and other strategies will be needed.
The aggregation of the neuronal protein alpha-synuclein (alpha-syn) is a key feature in the pathology of Parkinson's disease (PD). Alpha-syn aggregation has been suggested to be induced in the gut cells by pathogenic gut microbes such as Desulfovibrio bacteria, which has been shown to be associated with PD. This study aimed to investigate whether Desulfovibrio bacteria induce alpha-syn aggregation.
Fecal samples of ten PD patients and their healthy spouses were collected for molecular detection of Desulfovibrio species, followed by bacterial isolation. Isolated Desulfovibrio strains were used as diets to feed Caenorhabditis elegans nematodes which overexpress human alpha-syn fused with yellow fluorescence protein. Curli-producing Escherichia coli MC4100, which has been shown to facilitate alpha-syn aggregation in animal models, was used as a control bacterial strain, and E. coli LSR11, incapable of producing curli, was used as another control strain. The head sections of the worms were imaged using confocal microscopy. We also performed survival assay to determine the effect of Desulfovibrio bacteria on the survival of the nematodes.
Statistical analysis revealed that worms fed Desulfovibrio bacteria from PD patients harbored significantly more and larger alpha-syn aggregates than worms fed Desulfovibrio bacteria from healthy individuals or worms fed E. coli strains. In addition, during similar follow-up time, worms fed Desulfovibrio strains from PD patients died in significantly higher quantities than worms fed E. coli LSR11 bacteria. These results suggest that Desulfovibrio bacteria contribute to PD development by inducing alpha-syn aggregation.
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