New discovery! The cause of Parkinson's disease is not in the brain
- Apr 02, 2018 -

Parkinson's disease has long been considered to be a disease that originates in the brain. The movement of central neurons in the patient's brain gradually dies, resulting in tremors and loss of motor ability. But a new study published this week in the "Brain" scientific journal sheds light on another idea. The new study suggests that the primary cause of Parkinson's disease mutations may not be in the brain but in the peripheral immune system versus normal infections. Among the immune responses, the study provides a new understanding of Parkinson's disease.

Dr. Richard Smeyne, professor of developmental neurobiology at the St. Jude Children's Research Hospital, said, “We know that the brain cells of microglia can cause inflammation and eventually destroy the brain area and cause Parkinson’s movement to occur, but it’s not clear in this process. How common genetic mutations occur and whether this mutation alters microglia."

The postdoctoral fellow Elena Kozina of St. Jude Children's Research Hospital and Dr. Richard Smeyne studied the LRRK2 gene mutant. Mutations in the LRRK2 gene are the most common cause of hereditary Parkinson's disease. This genetic mutation is found in 40% of North African Arab descendants and 18% of Ashkenaziese descendants of PD. However, carrying the LRRK2 gene mutation itself is not sufficient to cause PD.

Dr. Elena Kozina said, “We know that if the twins carry mutations in the LRRK2 gene at the same time, they do not necessarily have Parkinson's disease. They also need a triggering event.”

Dr. Smeyne's previous research showed that the flu may increase the risk of Parkinson's disease. Based on this result, Dr. Smeyne decided to investigate whether the cause of Parkinson's disease is related to infection. Researchers use a bacterial shell called lippopolysaccharide (LPS), which can activate peripheral immune cells but cannot enter the brain through the blood-brain barrier itself, and activated immune cells do not migrate to the brain. On the surface it seems that LPS does not seem to have any direct effect on the brain.

When the researchers injected LPS into two of the most common LRRK2 gene-mutant mice, the immune response of these mice became a "cytokine storm," and the inflammatory mediators were elevated 3-5 times the normal response of LPS. Level. These inflammatory cytokines are secreted by T and B immune cells carrying the LRRK2 mutant gene.

Although LPS did not cross the blood-brain barrier, researchers found that elevated cytokines can enter the brain, creating an environment that causes microglial cells to activate and destroy the brain areas involved in the movement.

Dr. Smeyne said, "Although more tests are needed to prove this connection and to test whether humans do the same thing, these findings provide us with a new idea of the causes of Parkinson's disease. Although we cannot use immunosuppressants, Patients prevent this disease, but if this mechanism is confirmed, other interventions may effectively reduce the chances of developing this disease."

This article references:《Parkinson‘s gene initiates disease outside of the brain》