Myeloid-derived β-hexosaminidase is essential for neuronal health and lysosome function: implications for Sandhoff disease.

ABSTRACT: Lysosomal storage disorders (LSDs) are a large disease class involving lysosomal dysfunction, often resulting in neurodegeneration. Sandhoff disease (SD) is an LSD caused by a deficiency in the β subunit of the β-hexosaminidase enzyme (Hexb). Although Hexb expression in the brain is specific to microglia, SD primarily affects neurons. To understand how a microglial gene is involved in maintaining neuronal homeostasis, we demonstrated that β-hexosaminidase is secreted by microglia and integrated into the neuronal lysosomal compartment. To assess therapeutic relevance, we treated SD mice with bone marrow transplant and colony stimulating factor 1 receptor inhibition, which broadly replaced Hexb ^-/- microglia with Hexb-sufficient cells. This intervention

SUBMITTER: Tsourmas KI 

PROVIDER: S-EPMC11526954 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature