Bone morphogenetic proteins: New insights into their roles and mechanisms in CNS development, pathology and repair

Abstract

Bone morphogenetic proteins (BMPs) are a highly conserved and diverse family of proteins that play essential roles in various stages of development including the formation and patterning of the central nervous system (CNS). Bioavailability and function of BMPs are regulated by input from a plethora of transcription factors and signaling pathways. Intriguingly, recent literature has uncovered novel roles for BMPs in regulating homeostatic and pathological responses in the adult CNS. Basal levels of BMP ligands and receptors are widely expressed in the adult brain and spinal cord with differential expression patterns across CNS regions, cell types and subcellular locations. Recent evidence indicates that several BMP isoforms are transiently or chronically upregulated in the aged or pathological CNS. Genetic knockout and pharmacological studies have elucidated that BMPs regulate several aspects of CNS injury and repair including cell survival and differentiation, reactive astrogliosis and glial scar formation, axon regeneration, and myelin preservation and repair. Several BMP isoforms can be upregulated in the injured or diseased CNS simultaneously yet exert complementary or opposing effects on the endogenous cell responses after injury. Emerging studies also show that dysregulation of BMPs is associated with various CNS pathologies. Interestingly, modulation of BMPs can lead to beneficial or detrimental effects on CNS injury and repair mechanisms in a ligand, temporally or spatially specific manner, which reflect the complexity of BMP signaling. Given the significance of BMPs in neurodevelopment, a better understanding of their role in the context of injury may provide new therapeutic targets for the pathologic CNS. This review will provide a timely overview on the foundation and recent advancements in knowledge regarding the role and mechanisms of BMP signaling in the developing and adult CNS, and their implications in pathological responses and repair processes after injury or diseases.