帕金森氏症（Parkinson's disease, PD） 是一種慢性中樞神經系統退化疾病，主要為神經細胞的死亡影響運動神經系統，目前已知和神經元蛋白質組成路易氏體的過程有關。而最近，研究人員發現在帕金森氏症病患中免疫系統攻擊自身組織的第一個證據，研究結果也提出了透過抑制免疫反應的療法可以預防帕金森氏症神經元死亡的可能性。
study, led by scientists at Columbia University Medical Center (CUMC) and the
La Jolla Institute for Allergy and Immunology, was published today in Nature.
idea that a malfunctioning immune system contributes to Parkinson's dates back
almost 100 years," said study co-leader David Sulzer, PhD, professor of
neurobiology (in psychiatry, neurology and pharmacology) at CUMC. "But
until now, no one has been able to connect the dots. Our findings show that two
fragments of alpha-synuclein, a protein that accumulates in the brain cells of
people with Parkinson's, can activate the T cells involved in autoimmune
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."
once thought that neurons were protected from autoimmune attacks. However, in a
2014 study, Dr. Sulzer's lab demonstrated that dopamine neurons (those affected
by Parkinson's disease) are vulnerable because they have proteins on the cell
surface that help the immune system recognize foreign substances. As a result,
they concluded, T cells had the potential to mistake neurons damaged by
Parkinson's disease for foreign invaders.
new study found that T cells can be tricked into thinking dopamine neurons are
foreign by the buildup of damaged alpha-synuclein proteins, a key feature of
Parkinson's disease. "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 study, the researchers exposed blood samples from 67 Parkinson's disease
patients and 36 age-matched healthy controls to fragments of alpha-synuclein
and other proteins found in neurons. They analyzed the samples to determine
which, if any, of the protein fragments triggered an immune response. Little
immune cell activity was seen in blood samples from the controls. In contrast,
T cells in patients' blood samples, which had been apparently primed to
recognize alpha-synuclein from past exposure, showed a strong response to the
protein fragments. In particular, the immune response was associated with a
common form of a gene found in the immune system, which may explain why many
people with Parkinson's disease carry this gene variant.
Sulzer hypothesizes that autoimmunity in Parkinson's disease arises when
neurons are no longer able to get rid of abnormal alpha-synuclein. "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 attacked."
Sulzer and Sette labs are now analyzing these responses in additional patients,
and are working to identify the molecular steps that lead to the autoimmune
response in animal and cellular models.
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.
原文連結：Columbia University Medical Center. "Parkinson's is
partly an autoimmune disease, study finds. " ScienceDaily, 21 June, 2017.
Sulzer, Alessandro Sette et al., T
cells of Parkinson's disease patients recognize alpha-synuclein peptides.
Nature, 2017. DOI: 10.1038/nature22815