SORLA Orchestrates microglial dynamics for enhanced neuroprotection and recovery following ischemic stroke

This study identifies a novel function of Sortilin-related receptor with A-type repeats (SORLA), traditionally linked to Alzheimer's Disease (AD) as a high-risk gene and associated with neuronal function, in modulating microglial responses to ischemic stroke. We discovered that SORLA expression is significantly reduced in microglia following stroke, a change linked to increased brain injury and diminished neurological recovery. Utilizing SORLA knockout and overexpression models, we demonstrated its essential role in adjusting microglial inflammatory responses. Notably, microglial-specific overexpression of SORLA not only promoted anti-inflammatory actions and effective phagocytosis but also surpassed traditional concepts of microglial polarization. This overexpression mitigated brain damage and enhanced neurofunctional recovery post-stroke, highlighting the neuroprotective potential of SORLA. This breakthrough challenges the prevailing understanding the role of SORLA and opens new therapeutic possibilities for stroke recovery, indicating its wider relevance for neurodegenerative disease management.