How Do Proteins Cause Inflammation?
Proteins are an essential part of the body’s inflammatory response. In recent years, more and more attention has been given to the inflammation theory of disease. This is the idea that many diseases are caused by chronic inflammation. The theory posits that it’s possible to treat many diseases by interacting with the body’s inflammatory response.
Proteins cause inflammation by activating the inflammasome, a multiprotein complex found in immune cells. The inflammasome controls caspase-1 in the human body, an enzyme crucial to the immune system’s response to harmful microbes.
While inflammation is crucial in body functions, like healing wounds, it can overreact to naturally occurring proteins in the body. When the body’s inflammatory response overreacts, inflammatory diseases occur, like asthma, IBS, and other inflammation-linked conditions.
Why Do Protein Research?
To answer this question, it’s important to understand the central dogma of molecular biology. This principle states that genetic information flows in one direction within an organism. It begins in the DNA, which is replicated to create more DNA.
Then, the DNA is transcribed into RNA. There are many types of RNA, each with their own purpose. This includes functions like storing genetic blueprints, transcribing that genetic information, and creating ribosomes.
RNA is then translated into proteins that are used by the body as an energy source, muscle building blocks, cellular repair processes, and immune response. Proteins fuel important body functions, like the cellular repair process and immune responses. In other words, proteins are the closest genetic material to disease and our body's reactions to disease. With proteomics, researchers are able to see important factors of immune response.
In comparison, studying the genome might provide a lot of insights about genetic variants; however, if those variants aren’t used to create proteins later on, those genomic discoveries may not provide meaningful insights into disease processes.
Paving the way to early detection
In some inflammation-linked conditions, clinicians have to wait for onset of symptoms to make an accurate diagnosis. Proteomics research offers an opportunity to develop diagnostic tools that can identify diseases earlier. This will open the door to more timely treatment.
For example, several different viruses can cause a condition called viral encephalitis (VE). VE can cause seizures and consciousness disorders in patients as a consequence of the virus reaching the central nervous system and the host's inflammatory response. This leads to swelling in the brain. Diagnosis currently depends on the manifestation of symptoms.
In a 2022 study conducted by several Chinese research organizations, proteomic analysis was performed on 11 cerebrospinal fluid samples from patients with VE. Results identified 39 differentially expressed proteins, which may be the key to earlier diagnosis and intervention.
Alzheimer's disease is one of the most infamous inflammation-linked medical conditions. Like viral encephalitis, its diagnosis has historically depended on the onset of symptoms. This is complicated by the fact that Alzheimer's disease symptoms overlap significantly with those of other forms of dementia.
More and more, proteomics studies are examining how brain proteins change during the disease. With these results, researchers will be able to develop better screenings for Alzheimer’s disease and better therapeutic treatments. In a 2023 Brain study, for example, Swedish researchers identified the glial fibrillary acidic protein (GFAP) as a potential biomarker of Alzheimer's disease. GFAP is present in the blood at elevated levels a decade before the onset of symptoms. This discovery could lead to the creation of blood screenings for early detection of hereditary Alzheimer's disease.
Disease prognosis and monitoring
For some diseases, proteome screenings can provide insight into how a patient will react to treatment. In breast cancer patients, biopsy samples have been used to quantify the probability of cancer recurrence. The study analyzed 146 proteins and divided breast cancer into six different groups with unique recurrence-free survival (RFS) scores.
These results allowed for the creation of a 10-protein panel that can classify breast cancer patients into one of these six groups. This is promising for monitoring patients with breast cancer and managing their recurrence risk.
With more studies like this one, patients for many types of cancer will have better insight into both their current disease state and their future treatment needs.
Beyond disease monitoring & symptom management
For many proteomics studies, the goal goes beyond identifying disease biomarkers — these results will someday be used to develop novel treatments for disease. For example, more recent cancer studies identify inflammation as a hallmark of the disease. Inflammation is also conversely related to treatment success in cancer patients.
Some oral anti-inflammatories are already used in cancer treatment. Statins have been shown to decrease the effects of inflammatory cytokines and other proteins. Similarly, general anti-inflammatory drugs like ibuprofen have been proven to reduce adenocarcinomas and other cancers.
More targeted medications are a goal for protein research in cancer treatment. The microenvironment of cancer tumors is increasingly a target for treatment. A November 2022 review in Seminars in Cancer Biology identified anti-inflammatory nano-medicines as strong options for cancer treatment. With this option, anti-inflammatory drugs would be delivered directly to the cancerous cells.
Proteomics is also being employed to identify mechanisms behind incurable inflammatory diseases. In those cases, symptom management is often the only available treatment.
In traumatic brain injuries (TBIs), for example, we still know relatively little about the mechanisms that cause damage. RNA studies have not sufficiently explained TBIs; that's why a 2021 study used proteomics approaches to analyze protein expression after TBIs. The research identified 146 proteins that changed after a TBI, including 23 upregulated proteins and 16 fold changes.
By understanding the mechanisms underlying TBIs, treatments other than symptom management will be possible. Researchers in the same study reported that treating transthyretin upregulation with thyroxine resulted in alleviated brain edema and improved blood brain barrier integrity. With a better understanding of proteins' role in TBIs, novel treatments can be designed.
Proteomics is changing the landscape of disease and drug research. With more targeted information about disease pathogenesis and mechanisms, it will be possible to develop more effective and tailored treatment, diagnostics, and prognostics. As more advanced technologies develop, continued proteomics research is necessary to reach the full potential of personalized medicine.