Microglia-neuron crosstalk through Hex-GM2-MGL2 maintains brain homeostasis.

ABSTRACT: As tissue-resident macrophages of the central nervous system parenchyma, microglia perform diverse essential functions during homeostasis and perturbations¹. They primarily interact with neurons by means of synaptic engulfment and through the rapid elimination of apoptotic cells and non-functional synapses². Here, by combining unbiased lipidomics and high-resolution spatial lipid imaging, deep single-cell transcriptome analysis and novel cell-type-specific mutants, we identified a previously unknown mode of microglial interaction with neurons. During homeostasis, microglia deliver the lysosomal enzyme β-hexosaminidase to neurons for the degradation of the ganglioside GM2 that is integral to maintaining cell membrane organization and function. Absence of Hexb, encoding

SUBMITTER: Frosch M 

PROVIDER: S-EPMC12545202 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature