A joint research team of Yonsei and Korea universities’ medical schools has discovered that abnormalities in the trophoblast glycoprotein (TPBG) gene can cause Parkinson's disease.
The team identified the gene expression characteristics of TPBG in stem cells and mouse embryos and investigated the association between TPBG and Parkinson's disease in an adult mouse model.
Professors Kim Dong-wook and Park Sang-hyun of the Department of Physiology at Yonsei University College of Medicine and Professor Kim Dae-sung at Korea University College of Medicine jointly conducted the study.
The researchers found that the midbrain dopaminergic neurons derived from embryonic stem cells specifically expressed the TPBG genes. Subsequently, they confirmed that in the ventral midbrain, the region where midbrain dopaminergic neurons occur, also expressed TPBG during the process of mice growing into adults after fertilization.
The research team focused on the function of TPBG in midbrain dopaminergic cells as TPBG gene-deficient mice showed a selective loss of midbrain substantia nigra dopaminergic neurons as they grow old compared to normal mice.
In the midbrain substantia nigra of elderly TPBG gene-deficient mice, the team confirmed an increase in apoptosis, accompanied by mechanisms mainly seen in Parkinson's disease such as accumulation of alpha-synuclein and neuroinflammation.
Pathological findings of Parkinson's disease were also found in the striatum, a part of the brain innervated by dopaminergic neurons in the substantia nigra in the midbrain and secretes dopamine.
The striatum of aged TPBG gene-deficient mice showed axonal swelling and spheroids in dopaminergic nerve fibers. In addition, the team confirmed that the dopamine concentration reduced by about 30 percent compared to normal mice.
"The study suggests that TPBG plays an important function in the survival and maintenance of midbrain dopaminergic neurons, and if it does not function normally, it may increase the risk of developing Parkinson's disease," Professor Kim said. "Although we have yet to understand the clear pathogenesis of Parkinson's disease, the study is significant as the first to reveal that the TPBG gene is a new risk factor for inducing Parkinson's disease."
If companies conduct mechanism research and drug development targeting newly discovered risk factors, they will be one step closer to conquering Parkinson's disease, Kim added.
NPJ Parkinson's Disease published the study results in its online edition.