Astrocytes in Primary Familial Brain Calcification (PFBC): Emphasis on the Importance of Induced Pluripotent Stem Cell-Derived Human Astrocyte Models.

Abstract

Primary familial brain calcification (PFBC) is a rare, progressive central nervous system (CNS) disorder without a cure, and the current treatment methodologies primarily aim to relieve neurological and psychiatric symptoms of the patients. The disease is characterized by abnormal bilateral calcifications in the brain, however, our mechanistic understanding of the biology of the disease is still limited. Determining the roles of the specific cell types and molecular mechanisms involved in the pathophysiological processes of the disease is of great importance for the development of novel and effective treatment methodologies. There is a growing interest in the involvement of astrocytes in PFBC, as recent studies have suggested that astrocytes play a central role in the disease and that functional defects in these cells are critical for the development and progression of the disease. This review aims to discuss recent findings on the roles of astrocytes in PFBC pathophysiology, with a focus on known expression and roles of PFBC genes in astrocytes. Additionally, we discuss the importance of human astrocytes for PFBC disease modeling, and astrocytes as a potential therapeutic target in PFBC. Utilization of species-specific and physiologically relevant PFBC model systems can open new avenues for basic research, drug development, and regenerative medicine.