LA Jolla Institute (LJI) scientists have recently discovered that T-cells, known primarily as disease fighters, may also play a role in the development of Parkinson’s disease. The researchers, working in the laboratory of Professor Alessandro Sette Dr. biol., reported to MedicalXpress that Parkinson’s patients harbor T-cells that target key proteins such as alpha-synuclein and PINK1 found on brain cells. Alpha-synuclein is mostly found at the brain’s nerve cell endings. This protein releases neurotransmitters; however, it becomes problematic if it misfolds and forms Lewy body structures, such as those that are related to Parkinson’s disease.
PINK1 (PTEN-induced kinase 1) is a protein kinase primarily located in mitochondria. It plays a crucial role in mitochondrial quality control, protecting cells from stress-induced dysfunction. Mutations in the PINK1 gene are associated with early-onset Parkinson’s disease.
Dr. Sette and colleagues published the study earlier this year in npj Parkinsons Disease, identifying which subtypes of T-cells target alpha synuclein. Findings by the team provided clues showing that certain T-cells do indeed play a role in Parkinson’s.
The doctor commented that they were able to see the abnormal T-cells in patients after the patients were diagnosed with Parkinson’s, but so far, they have been at a loss to detect the disease earlier.
The Prodromal Period
In the new paper published in npj Parkinson’s Disease, Dr. Sette and his associates illustrate that harmful reactivity of T-cells is at its peak during the prodromal period, which is the early stage of a disease when it exhibits its first symptoms. However, the prodromal period may last for decades before symptoms such as cognitive impairment or tremors appear.
In the study, Dr. Sette and colleagues describe the potentially harmful T-cell reactivity as highest in the years before patients are presented with a definite diagnosis. Dr. Sette suggested that T-cell immunity could be a marker for treatment even before people exhibit symptoms. There is reason to believe, he continued, that there may also be an improved outcome with earlier detection.
The LJI team focused on T-cell reactivity in the study volunteers who were at high risk of developing Parkinson’s. Most cells contain mitochondria but certain cells, such as red blood cells, may lack them entirely. It depends on a cell’s energy requirements.
Dr. Sette and his team confirmed the presence of harmful T-cells well before diagnosis. He noted that T-cell reactivity was at its highest prior to the appearance of motor symptoms and tremors. Dr. Sette offers a word of caution, noting that Parkinson’s is a complex disease, and the newly found research does not prove that T-cells are fully responsible for it. Therefore, he cautions against “jumping to conclusions.”
Many questions remain unanswered:
- Does the destruction of nerve cells cause autoimmunity or is the reverse true?
- What is the significance of reactivity being at its highest prior to diagnosis?
Moving forward, the researchers are hoping to locate specific T-cells that protect tissues, with hopes for answers that may help find ways to block inflammation and protect brain cells.
