Gut infection triggers Parkinson’s-like symptoms in mice
Original article: Intestinal infection triggers Parkinson’s disease-like symptoms in Pink1(-/-) mice, Nature: July 17, 2019.
PINK1 has been linked to autophagy and the regulation of mitochondria. A new study shows that it may also protect cells, and the brain, from autoimmune attack.
Why is it important?
It adds to the growing body of literature on the link between gut pathology and infection and the emergence of Parkinson’s.
“If the findings of this study are independently replicated, they provide compelling evidence for a re-examination of the role of PINK1 (and other genes associated with Parkinson’s) in the context of this neurodegenerative condition.
It may also point towards novel potential therapeutic opportunities and an important step forward in our understanding of the condition.”
PINK1 and PARKIN are two genes that code for proteins that are essential for autophagy, that is, the appropriate destruction of dysfunctional organelles within the cell. When these proteins are absent, damaged mitochondria, which are the powerhouses of the cell, accumulate causing further damage. These genes are also implicated in genetic forms of Parkinson’s, but there is mounting evidence that these may be involved in the emergence of idiopathic Parkinson’s as well.
The Quebec based team investigated another aspect of PINK1 function, this time related to immunity. Their earlier findings had shown that PINK1 is actually involved in protecting cells containing degraded mitochondria from being attacked by the immune system in the presence of pathogens.
Mice lacking PINK1 due to gene knock out were given a solution which contained bacteria that normally cause gut infections, which resolved about 20 days later. However, this infection triggered a particular kind of immune cell to present a mitochondrial fragment on its surface which in turn triggers the immune system.
The team also found that the animals lacking PINK1 (which would normally protect them from such an autoimmune attach) showed subtle changes in the form and function of dopaminergic cells in the striatum, a critical region for movement which is also implicated in Parkinson’s. These animals had difficulties in coordination and overall reduced movement, which were improved by L-Dopa.
Intriguingly, these animals recovered fully from this short lived attack a year later, suggesting the damage was reversible.
In a separate set of experiments conducted on immune cells from the infected animals in a culture containing mitochondrial fragments, the researchers observed cytotoxic T cells which are involved in direct killing. These cells specifically target these mitochondrial fragments wherever they come across them. When these were then placed in the same culture as neurons and astrocytes from the PINK1 knockouts, the number of surviving dopaminergic neurons in particular declined.
This intriguing work would need to be followed up with more studies investigating the whole range of effects, including non-motor symptoms as a result of the interaction between loss of PINK1 and gut infection. It is also necessary to understand whether and how cytotoxic T cells, which are also found in the brain of people with Parkinson’s, gain access to the brain.
Original article: Matheoud D, Cannon T, Voisin A, Penttinen AM, Ramet L, Fahmy AM, Desjardins M. July 17, 2019. Intestinal infection triggers Parkinson’s disease-like symptoms in Pink1(-/-) mice