Is Parkinson’s An Autoimmune Disease?

In more Parkinson’s news, 2 genes associated with the disease have been found to be important immune system regulators

PINK1 and Parkin are two genes known to trigger Parkinson’s disease in some cases, and in a recent article we discussed the finding that they affect protein production too. Now, researchers have discovered they also have immune modulating effects, and that dyfunctional copies of each in dopaminergic neurons can lead to attack from the immune system. 

A novel function

A team of scientists from different institutions discovered that when both of these genes are dysfunctional, parts of these proteins are displayed on the cells’ surfaces following transfer from mitochondria, and that these act as beacons for immune cells. This activates T lymphocytes, which progressively destroy any cells exhibiting these antigens. 

“Clinicians have shown that the immune system is activated in the brain of PD patients. Our study explains how an attack by the immune system may be responsible for the destruction of dopaminergic neurons during the disease”

Parkinson’s disease involves a targeted destruction of dopaminergic neurons in a localised area, and while mitochondrial dysfunction and issues with protein production and packaging have been implicated in the disease, the new autoimmune theory makes a great deal of sense. This new connection has been validated in a mouse model, in which these two genes are missing. 

Dopaminergic neurons located in the substantia nigra are progressively destroyed in Parkinson’s disease

“While most laboratories are following the trail of the ‘toxic mitochondria’ model, our path led us to observe Parkinson’s disease from a different point of view. Our approach, centered on the immune system, led us down a different road where we were able to observe that autoimmunity is likely to play an important role in the progression of the disease”

Where do we go from here?

If this really is the case in humans, targeting these mitochondrial derived antigens could yield effective results. Further targeting of the vesicle packaging process that transports these antigens to the surface of the cell is also a viable option. 

“We think that our study is paradigm shifting because we have identified a new biological pathway linking mitochondria to immune mechanisms in Parkinson’s disease. This opens the possibility to use therapies based on modulation of the immune system, something already done for the treatment of other diseases. Interestingly, the role played by PINK1 and Parkin in limiting the presentation of mitochondrial antigens may not only regulate a process that impact Parkinson’s disease, but may also affect other autoimmune diseases like diabetes and lupus, and primary biliary cirrhosis, where a link to mitochondrial antigen presentation has been observed”

Read more at MedicalXpress