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Neurodegenerative diseases and the immune system
Neurodegenerative diseases, such as Parkinson’s, Alzheimer’s, Huntington’s, and Motor Neuron diseases, are generally thought of in their capacity as central and peripheral nervous system disorders. These diseases impact the motor skills, mental capacity, and quality of life of patients. While the cause of this neurodegeneration is largely unknown, scientists believe the immune system could be playing an important role.
Immune processes involved in neurodegeneration
Inflammation is an immune response to infection, injury, or illness. It involves the circulation of immune cells to affected sites to aid in defense and healing. However, in contrast to these acute examples of inflammation, which is resolved after a short period of time, some diseases involve chronic, or long-term, inflammation. This extended inflammation can eventually lead to the development of disorders after causing severe or permanent damage to the affected tissues and organs.
Chronic inflammation can be caused by disorders of the immune system or even viral infection. Viruses such as SARS-CoV-2 or HIV have a wide range of neuronal impacts that are still active areas of investigation. Chronic inflammation is also common in many autoimmune diseases, in
which the immune system routinely targets specific host tissues and organs. In these cases, immune cells are active in locations where no injury or infection is present, resulting in the attack or degeneration of healthy cells. Many people who have an autoimmune condition suffer from chronic inflammation that is generally treated with several classes of medications including steroids, non-steroidal anti-inflammatory drugs (NSAIDs), and disease-modifying anti-rheumatic drugs (DMARDs), as well as with immunosuppressant medications.
Inflammation is associated with multiple neurodegenerative diseases. Alzheimer’s disease has been linked to chronic inflammation, and specific genes involved in Parkinson’s disease have also been linked to the inflammatory response. Symptoms of Parkinson’s disease are exacerbated by inflammation, and studies have shown that certain inflammatory markers are present in the cerebrospinal fluid and blood of Parkinson’s patients. However, it is currently unknown whether inflammation in Parkinson’s is causative of or a result of the disease.
It has been hypothesized that neurodegeneration could be an autoimmune response, or perhaps a side-effect of an immune response elsewhere in the body. In Parkinson’s disease, one such trigger could be alpha-synuclein aggregates, protein clumps that are formed and deposited into brain tissue. Host protein aggregates pose a multifaceted problem, as the immune system won’t always recognize them as foreign.
Future therapies for immune system dysregulation
In a healthy and normally functioning state, the immune system has the ability to preserve balance between active immune responses and suppression of those responses, avoiding damage to the host. Included in this is a constant balance between inflammatory and anti-inflammatory responses, which is lost in some neurodegenerative diseases.
The goal of many therapeutics targeting the immune system is to slow the inflammatory response and control the role of the immune system in disease progression. Ideal intervention would minimize immune suppression at non-targeted sites, while limiting undesired inflammation at problem sites and tissues. When dealing with neurodegenerative disorders that are characterized by chronic inflammation in sensitive tissues, it would be ideal to administer therapeutic agents which halt the inflammatory response in the brain. Additionally, determining whether the inflammatory process is indicative of specific clinical symptoms and characteristics could be predictive of disease onset or rate of disease progression.
The immune system can also be leveraged to assist future therapeutic development. For example, in Parkinson’s disease, targeting the immune response to alpha-synuclein protein aggregates could aid in mitigating disease progression more effectively than blocking the accumulation of protein aggregates. Reducing inflammation could be essential for decreasing the rate of disease progression.