Postdoc Institute of Zoology, Chinese Academy of Sciences (CAS), Beijing, China
Abstract: Amyotrophic lateral sclerosis (ALS) is the most common adult-onset neurodegenerative disorder, leading to respiratory failure within 2-5 years of symptom onset. Dysfunctional microglia are believed to drive ALS progression exhibit functional heterogeneity across different disease stages, raising the critical question of whether stage-specific interventions using normal microglia replacement might yield varying therapeutic outcomes. Here, we demonstrate that restoring microglial function through systemic bone marrow transplantation followed by genetically normal microglia replacement reduced microglial activation, delayed symptoms progression, and extended survival in the SOD1G93A mouse model of ALS at both the presymptomatic stage and disease onset. Further analysis revealed this treatment restored crucial microglial-oligodendrocyte/OPCs communication and improved neuronal and oligodendrocyte health. Thus, microglia replacement emerges as a highly effective approach for preventing disease progression, offering potential therapeutic avenues for ALS.
