The time sequence of NG2 cell uptake of AB42 is similar to that of microglia. Based on our observation the ability of NG2 cells to clear AB is much weaker than microglia. Therefore, in AD brain, microglia is the major cell type to clear AB. Microglia expresses a number of putative AB transporters, such as scavenger receptor www.selleckchem.com/products/dorsomorphin-2hcl.html for advanced glycation end products formyl peptide receptor like 1 and toll like receptors. These trans porters may facilitate microglia induced clearance of AB. Mandrekar et al. also demonstrate that microglia uptake of AB is mediated by fluid phase macropino cytosis both in vitro and in vivo, and tubulin depoly merization and actin polymerization are required for the process. Our data support that NG2 cell mediated AB42 uptake depends on actin polymerization but not tubulin depolymerization.

Cytochalasin D does not completely inhibit AB42 intern alization in NG2 cells, Inhibitors,Modulators,Libraries suggesting that there may be other pathways that participate in AB42 internalization. AB can bind to various membrane biomolecules, including lipids, proteins and proteoglycans. A number of putative AB transporters have been Inhibitors,Modulators,Libraries identified, such as 7 nicotinic acetylcholine receptor, apolipoprotein E receptors, members of the low density lipo protein receptor family, scavenger receptor for advanced glycation end products, formyl peptide receptor like 1 and toll like recep tors. It is likely that AB also can be internalized through these Inhibitors,Modulators,Libraries receptors or transporters. Mechanisms of NG2 cell mediated AB42 degradation Recent studies suggest that autophagylysosome pathway is an important and perhaps compensatory mech anism for intracellular protein degradation.

The accumulation of Inhibitors,Modulators,Libraries lysosomes and their hydrolases within neurons is a well established neuropathologic Inhibitors,Modulators,Libraries feature of AD. The endosomal lysosomal system is reported to be activated in vulnerable neurons in AD brains. It has been suggested that the autophagylysosome pathway is involved in the degradation of AB. Autophago somes and other prelysosomal autophagic vacuoles were abundant in AD brains. The transport of autophagic vacu oles and their maturation to lysosomes is impaired, re sulting in the accumulations of immature autophagic vacuoles and the inhibition of AB clearance. We showed that AB42 was localized to lysosomes after intern alization and the expression levels of lysosomal associated membrane protein 1 and 2 genes were increased.

More over, the degradation of AB42 was inhibited by lysosomal proteolysis inhibitors leupeptin and pepstatin A. The ef fects of leupeptin supports the role of cysteine protease in degrading AB has been documented in earlier studies. Pepstatin A increased AB42 levels without http://www.selleckchem.com/products/AG-014699.html altering LC3 II or beclin1 levels. This may be due to the relative insensitivity of NG2 cells to pepstatin A and a higher con centration may be necessary.