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Study Hints that Immune System May Attack Cells in Parkinsonís

A new study suggests that Parkinson’s disease (PD) may, in part, be an autoimmune disorder – a disease in which a person’s immune system mistakenly attacks the body’s own cells.  If further research upholds this idea, it may lead to new approaches to preventing the brain cell death that underlies PD.  The report appears in the April 16 edition of Nature Communications.

In diseases such as type I diabetes and multiple sclerosis, a person’s immune system cells attack and kill specific cell types in the body.  The immune system knows which cells to attack because of a sort of molecular flag, called an antigen, which sits on a “flagpole” called an MHC.  Scientists have long believed that neurons affected by PD were protected from attack by the immune system because they do not have the flagpoles, the MHCs.

Led by David Sulzer, Ph.D., Carolina Cebrián, Ph.D., and her colleagues at the PDF Research Center at Columbia University Medical Center, knew that MHCs had been discovered on rodent neurons.  So they investigated whether the conventional wisdom was wrong – whether human brain cells might, in fact, have MHCs too.  First they examined postmortem brain tissue from healthy donors and from people who had lived with PD.  They also studied mouse neurons and human neurons to test whether stresses similar to PD could stimulate the neurons to use the MHC to display antigens.

Results

  • In the brain tissue samples, the researchers found an MHC called MHC-1 in neurons from two distinct brain regions affected by PD, dopamine neurons in a brain region called the substantia nigra and neurons in the brain’s locus coeruleus.
  • In the laboratory, dopamine neurons derived from human and mouse stem cells were able to make MHC-1.  
  • Under certain circumstances – including conditions known to occur in Parkinson’s – these dopamine neurons used the MHC-1 “flagpole” to display antigens. 
  • Among the different types of neurons tested, the two types affected in Parkinson’s were far more responsive to signals that triggered antigen display than other neurons.
  • In further experiments, the scientists showed that immune system cells (T cells) recognized and killed neurons displaying specific antigens.

What Does It Mean?

The role of the immune system in PD, if any, is very controversial. The authors in this study showed that the immune system may have a greater role in PD than previously ascribed to it. The researchers have shown in this study, that the molecules required for dopamine cells and immune cells to interact are indeed present on the surface of the dopamine cells. Theoretically, these molecules can be involved in a cascade that would lead to dopamine cell death. Whether this actually happens in brains of people with PD remains unknown. 

If scientists can demonstrate that certain immune cells attack and kill neurons in people with PD, it will open the door to new approaches to preventing neuronal death similar to treatments for autoimmune diseases and halting Parkinson’s disease.

Reference: Cebrián C, Zucca FA, Mauri P, Steinbeck JA, Studer L, Scherzer CR, Kanter E, Budhu S, Mandelbaum J, Vonsattel JP, Zecca L, Loike JD, Sulzer D (2014) MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration. Nat Comms 5:3633. DOI: 10.1038/ncomms4633 http://dx.doi.org/10.1038/ncomms4633

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Source Date: Jun 02 2014