Selected Grantee Publications

PGRN Deficiency Exacerbates, Whereas a Brain Penetrant PGRN Derivative Protects, GBA1 Mutation–Associated Pathologies and Diseases

Zhao et al., Proc Natl Acad Sci USA. 2023.

https://www.pnas.org/doi/10.1073/pnas.2210442120

Mutations in GBA1 are associated with Gaucher disease (GD) and are also genetic risks in developing Parkinson’s disease (PD). Investigators created a mouse model and demonstrated that progranulin (PGRN) deficiency in Gba1 mutant mice caused early onset and exacerbated GD phenotypes, leading to substantial increases in substrate accumulation and inflammation in visceral organs and the central nervous system. These in vivo and ex vivo data demonstrated that PGRN plays a crucial role in the initiation and progression. In addition, the mouse model provides a clinically relevant system for testing therapeutic approaches for GD and PD. Supported by ORIP (R21OD033660), NIAMS, and NINDS.