Parkinson’s disease (PD) is a movement disorder caused by progressive degeneration of the midbrain dopaminergic (mDA) neurons in the substantia nigra pars compacta (SNc). Despite intense research efforts over the past decades, the etiology of PD remains largely unknown. Here, we discovered the involvement of trophoblast glycoprotein (Tpbg) in the development of PD-like phenotypes in mice. Tpbg expression was detected in the ventral midbrain during embryonic development and in mDA neurons in adulthood. Genetic ablation of Tpbg resulted in mild degeneration of mDA neurons in aged mice (12–14 months) with behavioral deficits reminiscent of PD symptoms. Through in silico analysis, we predicted potential TPBG-interacting partners whose functions were relevant to PD pathogenesis; this result was substantiated by transcriptomic analysis of the SNc of aged Tpbg knockout mice. These findings suggest that Tpbg is a new candidate gene associated with PD and provide a new insight into PD pathogenesis.
Bibliographical noteFunding Information:
This work was supported by (1) the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI18C0829); (2) a Korea University Research Grant; and (3) BK21 PLUS Program for Biotechnology, Korea University. This work was conducted in part at the Yonsei Advanced Imaging Center in cooperation with Carl Zeiss Microscopy, Yonsei University College of Medicine, and artistically supported by Medical Illustration & Design, part of the Medical Research Support Services of Yonsei University College of Medicine.
© 2021, The Author(s).
ASJC Scopus subject areas
- Clinical Neurology
- Cellular and Molecular Neuroscience