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Background Our laboratories forged the concept of macrophage delivery of protein antioxidants to attenuate neuroinflammation and nigrostriatal degeneration in Parkinson’s disease (PD). Notably, the delivery of the redox enzyme, catalase, incorporated into a polyion complex micelle (“nanozyme”) by bone marrow-derived macrophages protected the nigrostriatal against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication. Nonetheless, how macrophage delivery of nanozyme increases the efficacy of catalase remains unknown. Methods Herein, we examined the transfer of nanozyme from macrophages to brain microvessel endothelial cells, neurons and astrocytes. Results Facilitated transport of the nanozyme from macrophages to endothelial and neural target cells occurred through endocytosis-independent mechanisms that involved fusion of cellular membranes; macrophage bridging conduits; and nanozyme lipid coatings. Nanozyme transfer was operative across an artificial blood brain barrier and showed efficient reactive oxygen species decomposition. Conclusion This is the first demonstration that drug-loaded macrophages discharge particles to contiguous target cells for potential therapeutic brain enzyme delivery. The pathways for drug delivery shown may be used for the treatment of degenerative disorders of the nervous system.

Methionine aminopeptidase type 1 (MetAP1) cotranslationally removes N-terminal methionine from nascent polypeptides, when the second residue in the primary structure is small and uncharged. Eukaryotic MetAP1 has an N-terminal zinc finger domain not found in prokaryotic MetAPs. We hypothesized that the zinc finger domain mediates the association of MetAP1 with the ribosomes and have reported genetic evidence that it is important for the normal function of MetAP1 in vivo. In this study, the intracellular role of the zinc finger domain in yeast MetAP1 function was examined. Wild-type MetAP1 expressed in a yeast map1 null strain removed 100% of N-terminal methionine from a reporter protein, while zinc finger mutants removed only 31-35%. Ribosome profiles of map1 null expressing wild-type MetAP1 or one of three zinc finger mutants were compared. Wild-type MetAP1 was found to be an 80S translational complex-associated protein that primarily associates with the 60S subunit. Deletion of the zinc finger domain did not significantly alter the ribosome profile distribution of MetAP1. In contrast, single point mutations in the first or second zinc finger motif disrupted association of MetAP1 with the 60S subunit and the 80S translational complex. Together, these results indicate that the zinc finger domain is essential for the normal processing function of MetAP1 in vivo and suggest that it may be important for the proper functional alignment of MetAP1 on the ribosomes.