Table 1.
Effects of pretreatment with memantine on the expression of phagocytosis-related proteins in mouse 6–3 microglial cells measured using flow cytometry.
| Effects of memantine | Function in microglial cells | References |
|---|---|---|
| Potentiation | ||
| ABCA7 | ABCA7 is important for microglial phagocytic activity. Deletion of ABCA7 in AD mouse exacerbates cerebral Aβ plaque load | 28,29 |
| ADAMTS4 | ADAMTS4 increases the number of microglia expressing arginase-1, a marker of anti-inflammatory functions in the ischemic brain | 27 |
| No effect | ||
| TREM2 | TREM2 promotes proliferation and enhances phagocytosis of microglia, while recent reports suggesting a complex action of TREM2 on inflammatory processes because of both pro- or anti-inflammatory properties | 6,23 |
| DAP12 | Adaptor protein gets phosphorylated, recruits SYK, and activates intracellular pathways such as PI3K and/or MAPK when binding to TREM2 ligands | 24,25 |
| Neprilysin | Microglia can phagocytose Aβ and also clear Aβ by degradation via Aβ degrading proteases, neprilysin | 26 |
| CX3CR1 | Microglial activity is restrained by fractalkine (CX3CL1) derived from neurons and cognate receptors on microglia, CX3CR1, in normal brain | 42 |
| CR3(CD11b/c) | CR3 is surface complement receptor involved in clearance of weak synapses mediated by microglial phagocytosis | 43 |
| CD68 | CD68, a lysosomal/endosomal associated membrane glycoprotein, is a marker for either activated and/or senescent microglia | 44 |
| Dectin-1/Clec7a | Dectin-1/Clec7a is a pattern recognition receptor involved in the microglial phagocytosis of beta-glucan particles | 45 |
| PTGEs (Prostaglandin E synthase) | PTGEs produces eicosanoid prostaglandin E2 (PGE2) which plays important roles in neuroinflammation and AD brain | 46 |
| Socs3 (suppressor of cytokine signaling 3) | SOCS3 suppresses JAK/STAT3 pathway resulting in cytokine signaling and has anti-inflammatory roles in the brain of AD mouse | 47,48 |
| ADAM10 | ADAM10, one of four loci recently identified as risk genes of AD, is expressed in microglia and it cleaves CX3CL1 into a secreted form to remodel synapses | 49,50 |
| ADAM17 | ADAM17 inhibits clearance of apoptotic cells by microglia while it potentiates cleavage of amyloid precursor protein resulting in reduction of Aβ generation | 51,52 |
| Suppression | ||
| None | ||