| First Author | Lee HY | Year | 2025 |
| Journal | Signal Transduct Target Ther | Volume | 10 |
| Issue | 1 | Pages | 295 |
| PubMed ID | 40931022 | Mgi Jnum | J:385836 |
| Mgi Id | MGI:8297604 | Doi | 10.1038/s41392-025-02398-2 |
| Citation | Lee HY, et al. (2025) Astrocytic monoamine oxidase B (MAOB)-gamma-aminobutyric acid (GABA) axis as a molecular brake on repair following spinal cord injury. Signal Transduct Target Ther 10(1):295 |
| abstractText | Neuroregeneration and remyelination rarely occur in the adult mammalian brain and spinal cord following central nervous system (CNS) injury. The glial scar has been proposed as a major contributor to this failure in the regenerative process. However, its underlying molecular and cellular mechanisms remain unclear. Here, we report that monoamine oxidase B (MAOB)-dependent excessive gamma-aminobutyric acid (GABA) release from reactive astrocytes suppresses the CNS repair system by reducing brainderived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) expression in severe spinal cord injury (SCI) animal models. Genetic deletion of MAOB in a mouse SCI model promotes both functional and tissue recovery. Notably, the selective MAOB inhibitor, KDS2010, facilitates recovery and regeneration by disinhibiting the BDNF-TrkB axis in a rat SCI model. Its dose-dependent effects were further validated in a monkey SCI model. Moreover, KDS2010 demonstrated a tolerable safety profile and dose-proportional pharmacokinetics in healthy humans during a phase 1 clinical trial. This pathway therefore represents a pivotal target for overcoming the intrinsic barriers to CNS repair after injury. Our findings identify the astrocytic MAOBGABA axis as a crucial molecular and cellular brake on the CNS repair system following SCI and highlight the translational potential of KDS2010 as a promising therapeutic candidate for SCI treatment. |
