RanBP9 promotes mitochondrial dysfunction and calcium deregulation in primary neurons

Abstract

soluble As aggregates revealed high levels of high-molecular weight Asoligomers and protofibrils (hiMWAs) in APP23 and APP51/16 mice. Using native (BN-PAGE) and denaturing (SDS-PAGE) protein analysis all types of As-aggregates occurring in APP23 mice were also observed in APP51/16 mice. The major difference between APP23 and APP51/16 mice was that APP23 mice exhibited higher levels of easily denaturable As-aggregates than APP51/16 mice. Conclusions: These results indicate that high levels of soluble, denaturable As-aggregates are related to dendritic and synapse degeneration in APP23 mice whereas low levels of these aggregates, as well as As-plaque deposition, had no effect on the integrity of the neurons in APP51/16 mice. Thus, the concentration of soluble, denaturable As-aggregates is related to its toxicity and acidic neurotransmitters can be discussed to cause denaturation of these aggregates and release of presumably toxic low-molecular weight oligomers. Supported by DFG and AFI.