There is growing evidence of the role of the immune system in Parkinson's

In a special issue of the Journal of Parkinson's Disease, The Immune System for Parkinson's Disease, experts highlight recent research breakthroughs in the link between immune activation, neuroinflammation, and Parkinson's disease (PD), and discuss challenges and new therapeutic strategies targeting the immune system in hopes of reducing or reversing neurodegeneration
.

Although multiple independent studies have provided evidence of the involvement of central and peripheral immune and inflammatory processes in PD, the causal relationship between neuroinflammation and neurodegeneration in PD is difficult to establish because initial events can occur many years
before neuronal loss and clinical manifestations appear.
However, there is growing evidence that inflammation may be the cause of PD rather than a consequence or by-occurrence
of neurodegenerative processes.

Guest editors Bastiaan R.
Bloem, MD, Patrik Brundin, MD, Ashley Harms, MD, Cecilia Lindestam Arlehamn, MD, Eng King Tan, MD, and Caroline Williams-Gray, MD, commented, "PD risk is influenced by many factors, including a mix of immunogenetics and environment, such as infection history
。 "In recent years, there has been increasing evidence that PD is associated
with autoimmune conditions, the immune system, or its abnormal responses, both in PD patients and in various experimental models.
"

Topics covered in this addendum include:

• Immunogenetic determinants of PD

• Epidemiological evidence for immune components of Parkinson's disease

• Infection and microbiota effects

• Link between GBA1 gene and immune alterations in PD

• Role of T lymphocytes

• Role of B lymphocytes

• Natural killer cells in Parkinson's disease

• Age-related immune changes in Parkinson's disease

• Microglia activation in the brains of patients with neurodegenerative diseases, including PD

• Current evidence and knowledge gaps regarding inflammasome activation in PD

• The role of central and peripheral inflammation

• Prodromal symptoms of neuroinflammation and immune changes in PD

• PD inflammatory animal models

• Biomarkers of inflammation in PD

• Therapeutic strategies that target the immune system of PD patients

Patients with PD and other concleopathies often exhibit autoimmune features, including forms of immune cells (CD4+ and CD8+ T lymphocytes) recognizing α-conuclein
.
A review article by Benjamin D.
Hobson, M.
D.
, and David Sulzer, Ph.
D.
, of Columbia University Irving Medical Center focused on how peripheral T lymphocytes enter brain regions
primarily affected by Parkinson's disease.
Neurons in these brain regions can present antigens that bind to MHC class 1 molecules on the cell surface and signal the physiological state of the cell to immune cells such as T cells
.
Certain subtypes of T cells (CD8+) have been shown to bind to antigens: MHC class 1 complexes on the cell surface, which promote further immune responses, leading to cell damage and, ultimately, neuronal death
.

"Recent animal models suggest the possibility that T cells in PD have self-reacting to mitochondrial antigens," Dr.
Sulzer noted
.
"However, it is unclear whether neuroantigen presentation plays a role in Parkinson's disease or other neurodegenerative diseases, and we are working to better understand the potential impact
of autoimmune responses on neurodegenerative diseases.
"

"In summary, multiple independent studies in clinical and preclinical models provide conclusive evidence that central and peripheral immune and inflammatory processes are involved in PD," the guest editor noted
.
"Our understanding of how the immune system contributes to the pathogenesis of Parkinson's disease is evolving, with growing evidence of the role
of several genes and susceptibility sites.
"

A major challenge is to use this data and knowledge to identify specific targets within the immune system or target major disease-causing proteins involved in abnormal immune responses; and it is possible to identify a subset of
patients who are more responsive to immunomodulatory therapy.

"Clinical trials against α-synuclein have begun, and clinical and experimental trials focusing on different immune components are ongoing," commented Bastiaan R.
Bloem, Ph.
D.
, co-guest editor and co-editor-in-chief of JPD, MD of the Parkinson's and Movement Disorders Specialty Center at Nemegen University Medical Center
.

The guest editor highlights that much more research is needed to determine the individual and collective roles of individual immune cells (and their subpopulations) and how they interact within the neurovascular unit, with α-synuclein and other key proteins
.

Professor Bloem concluded: "Longitudinal studies using molecular imaging to measure microglial activation in the brain, as well as detailed blood and CSF immune function tests and phenotypic analysis of high-risk subjects or prodromal Parkinson's disease, may find key clues
to the temporal causal relationship between neuroinflammation and Parkinson's disease.
"

Parkinson's is a slow-moving disease that affects movement, muscle control, and balance
.
It is the second most common age-related neurodegenerative disease, affecting about 3% of the 65-year-old population and up to 5% of people
over the age of 85.