- Parkinson's disease is a neurodegenerative disorder that leads to
death of dopamine neurons in the brain, with the cause still not clearly
- Current study suggests that autoimmunity may play a part in the
death of dopamine neurons in Parkinson's disease.
attack of the dopamine neurons could contribute at least in part to Parkinson's
disease (PD), according to a recent study undertaken by scientists at Columbia
University Medical Center (CUMC) and the La Jolla Institute for Allergy and
Immunology. The study
was published today in Nature
Disease - Unfolding the Mystery
has been believed for over a 100 years that a dysfunctional immune system could
be one of the factors causing Parkinson's disease
. However, no clear role or
probable mechanism has been demonstrated.
‘Therapies that suppress the immune response may be potentially useful in preventing neuronal death in Parkinsonís disease.’
treatment is mainly symptomatic; with no clear clues as to the cause, the cure
for PD still remains elusive.
findings of the current study suggest that at
least 2 fragments of alpha synuclein, an abnormal protein that accumulates in
the dopaminergic neurons, could trigger the T cells involved in autoimmune
"It remains to be seen whether the
immune response to alpha-synuclein is an initial cause of Parkinson's, or if it
contributes to neuronal death and worsening symptoms after the onset of the
disease," said study co-leader Alessandro Sette, Dr. Biol. Sci., professor
in the Center for Infectious Disease at La Jolla Institute for Allergy and
Immunology in La Jolla, Calif. "These findings, however, could provide a much-needed diagnostic test
for Parkinson's disease
, and could help us to identify individuals at risk or
in the early stages of the disease."
Role of Abnormal Alpha Synuclein Accumulation - The Study
- The study team compared blood samples (containing immune T cells)
from 67 Parkinson's disease patients with 36 age-matched healthy controls
not suffering from the disease.
- These blood samples were exposed to fragments of alpha synuclein, a
protein found in the brain cells to determine whether these fragments
stimulated any immune response.
- Little or no immune activity was noted in the control blood samples.
- In contrast, in the PD patients, a strong immune response was noted
against the alpha synuclein fragments as the T cells in these patients had
been sensitized to recognize and attack alpha synuclein.
- Also, the immune response was associated with the presence of a
common gene variant that occurs in the immune system; many PD patients are
found to have this gene variant.
findings of the study suggest that the immune
T-cells are tricked
into perceiving the damaged dopamine neurons in PD (due
to abnormal accumulation of alpha synuclein) as foreign, and attacking them,
leading to their death.
"In most cases of Parkinson's,
dopamine neurons become filled with structures called Lewy bodies, which are
primarily composed of a misfolded form of alpha-synuclein," said Dr.
Sulzer. 'The results raise the possibility that Parkinson's is partly an
autoimmune disease, Dr. Sulzer says, but more research is needed to confirm the
Also Carry Surface Antigens Recognized By the Immune System
recently, it was thought that all neurons are protected from immune attack,
since they do not carry any antigens on their surface, and thus cannot be
recognized by immune T cells.
earlier research by Dr. Sulzer and his team has shown that certain neurons including the dopamine neurons, affected in Parkinson's
disease, do carry proteins on their surface that enable their recognition by
immune T cells
. These neurons are
therefore vulnerable to immune attack and death which is what happens in PD.
Abnormal Alpha Synuclein Accumulates In The First Place
increasing age, the scavenging mechanism
of the dopamine neurons fails to get rid of the alpha synuclein
accumulates and triggers the autoimmune response leading to Parkinson's
"Young, healthy cells break down and
recycle old or damaged proteins," he said. "But that recycling
process declines with age and with certain diseases, including Parkinson's. If
abnormal alpha-synuclein begins to accumulate, and the immune system hasn't seen
it before, the protein could be mistaken as a pathogen that needs to be
Expanding the Scope of the Current Study
The study team is analyzing these autoimmune responses in more patients. They are working to determine the possible
molecular mechanisms involved in the autoimmune response in animal and cellular
models to gain more insight into the possible pathogenesis of PD.
"Our findings raise the possibility
that an immunotherapy approach could be used to increase the immune system's tolerance for
alpha-synuclein, which could help to ameliorate or prevent worsening symptoms in Parkinson's disease
patients," said Dr. Sette.Source: Medindia